中文版 | English

Functional Study of EYA1 in Glioma Formation and Progression

Name pinyin
WEI Tianzi
School number
Mentor unit
Tutor of External Organizations
Tutor units of foreign institutions
Publication Years
Submission date
Place of Publication

Glioma is the most common intracranial tumor, and it constitutes more than half of brain tumors. It is also the leading cause of cancer death worldwide. Infiltrative growth of glioma cells makes it difficult to remove whole tumor and results in inadequate therapeutic response and high recurrence. Understanding the functional implications and interplay of molecular changes and elucidating the molecular drivers underlying glioma formation and progression are among the priority of glioma research.

EYA1 is a protein with dual functions. It serves as a transcription cofactor and a phosphatase. EYA1 regulates cell proliferation, survival, and tissue specification, and it is required for normal cranial facial morphogenesis as well as embryonic development of inner ear, kidney, and lung. The reactivation of EYA1 is also involved in numerous tumor formation and development processes. For example, EYA1 has been reported to control gliomagenesis through transcriptionally regulating MYC to maintain glioblastoma stem cell stemness and survival. However, the function of EYA1 in non-stem-like glioma cells is still unclear.

To date, γH2AX, c-Myc, and Notch1 have been identified to be directly dephosphorylated by EYA1 in different biological contexts. However, the substrates specifically related to glioma remains to be recognized. Also, EYA1-centered interactome and targetome have not been uncovered in glioma. The relationship between the EYA1 expression and glioma prognosis is not well understood.

In this study, we firstly systematically analyzed EYA1 expression patterns in different tumors and normal tissues and found that EYA1 served as a novel marker in glioma. EYA1 was explicitly upregulated in oligodendroglioma tumors with IDH mutation and 1p/19q codeletion, and EYA1 expression was positively correlated with patient survival. Our patient tissue array data also suggested that EYA1 expression was elevated in glioma samples and correlated with glioma grades. We further investigated the function of EYA1 in glioma cell growth in vitro and in vivo, and we found that EYA1 suppression inhibited glioma cell proliferation, clonogenicity, tumorsphere formation, and tumor formation, but extended the survival time of mice bearing glioma.

Mechanistically, we uncovered EYA1-regulated interactome, targetome, and phosphoproteome through affinity-mass spectrometry, RNA sequencing, and phosphoproteomics techniques and systematically determined the downstream targets of EYA1 in glioma cells. We found that EYA1 mainly interacted with factors related to cell cycle regulation and DNA damage repair. Transcriptome data also suggested that EYA1 inhibition downregulated the expression of genes related to cell cycle progression, including CCND1, CDKN1A, CDKN1B, and E2F3. Our experimental data also indicated that EYA1 suppression made cell cycle arrest at the G1 phase. Finally, our phosphoproteome results suggested that BCL2L12, a well-known oncogene in glioma, was a potential substrate of EYA1. Moreover, we validated that EYA1 dephosphorylated BCL2L12 at Thr33 to stabilize it by preventing its ubiquitination, which enhances BCL2L12-mediated cell growth and apoptosis resistance in glioma.

In summary, we systematically studied the role of EYA1 in regulating cell growth during glioma formation and progression in this thesis. Our study may provide a new therapeutic target for glioma.

Training classes
Enrollment Year
Year of Degree Awarded
References List

Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samson, D., Vincent, C., Levi-Acobas, F., Cruaud, C., Le Merrer, M., Mathieu, M., et al. (1997a). Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1. Hum Mol Genet 6, 2247-2255.Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., et al. (1997b). A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet 15, 157-164.Ahmed, M., Xu, J., and Xu, P.X. (2012). EYA1 and SIX1 drive the neuronal developmental program in cooperation with the SWI/SNF chromatin-remodeling complex and SOX2 in the mammalian inner ear. Development 139, 1965-1977.Alcantara Llaguno, S., Chen, J., Kwon, C.H., Jackson, E.L., Li, Y., Burns, D.K., Alvarez-Buylla, A., and Parada, L.F. (2009). Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15, 45-56.Alvarez-Breckenridge, C.A., Yu, J., Price, R., Wojton, J., Pradarelli, J., Mao, H., Wei, M., Wang, Y., He, S., Hardcastle, J., et al. (2012). NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nat Med 18, 1827-1834.Alves, J.A., Barone, P., Engelender, S., Froes, M.M., and Menezes, J.R. (2002). Initial stages of radial glia astrocytic transformation in the early postnatal anterior subventricular zone. J Neurobiol 52, 251-265.Anantharajan, J., Zhou, H., Zhang, L., Hotz, T., Vincent, M.Y., Blevins, M.A., Jansson, A.E., Kuan, J.W.L., Ng, E.Y., Yeo, Y.K., et al. (2019). Structural and Functional Analyses of an Allosteric EYA2 Phosphatase Inhibitor That Has On-Target Effects in Human Lung Cancer Cells. Mol Cancer Ther 18, 1484-1496.Auvergne, R.M., Sim, F.J., Wang, S., Chandler-Militello, D., Burch, J., Al Fanek, Y., Davis, D., Benraiss, A., Walter, K., Achanta, P., et al. (2013). Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes. Cell Rep 3, 2127-2141.Azuma, N., Hirakiyama, A., Inoue, T., Asaka, A., and Yamada, M. (2000). Mutations of a human homologue of the Drosophila eyes absent gene (EYA1) detected in patients with congenital cataracts and ocular anterior segment anomalies. Hum Mol Genet 9, 363-366.Bachoo, R.M., Maher, E.A., Ligon, K.L., Sharpless, N.E., Chan, S.S., You, M.J., Tang, Y., DeFrances, J., Stover, E., Weissleder, R., et al. (2002). Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1, 269-277.Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., Dewhirst, M.W., Bigner, D.D., and Rich, J.N. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756-760.Birk, H.S., Han, S.J., and Butowski, N.A. (2017). Treatment options for recurrent high-grade gliomas. CNS Oncol 6, 61-70.Bleau, A.M., Hambardzumyan, D., Ozawa, T., Fomchenko, E.I., Huse, J.T., Brennan, C.W., and Holland, E.C. (2009). PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 4, 226-235.Boija, A., Klein, I.A., Sabari, B.R., Dall'Agnese, A., Coffey, E.L., Zamudio, A.V., Li, C.H., Shrinivas, K., Manteiga, J.C., Hannett, N.M., et al. (2018). Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains. Cell 175, 1842-1855 e1816.Bonini, N.M., Leiserson, W.M., and Benzer, S. (1993). The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 72, 379-395.Boots-Sprenger, S.H., Sijben, A., Rijntjes, J., Tops, B.B., Idema, A.J., Rivera, A.L., Bleeker, F.E., Gijtenbeek, A.M., Diefes, K., Heathcock, L., et al. (2013). Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution. Mod Pathol 26, 922-929.Bowman, R.L., Klemm, F., Akkari, L., Pyonteck, S.M., Sevenich, L., Quail, D.F., Dhara, S., Simpson, K., Gardner, E.E., Iacobuzio-Donahue, C.A., et al. (2016). Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies. Cell Rep 17, 2445-2459.Buchlak, Q.D., Esmaili, N., Leveque, J.C., Bennett, C., Farrokhi, F., and Piccardi, M. (2021). Machine learning applications to neuroimaging for glioma detection and classification: An artificial intelligence augmented systematic review. J Clin Neurosci 89, 177-198.Bui, Q.T., Zimmerman, J.E., Liu, H., and Bonini, N.M. (2000). Molecular analysis of Drosophila eyes absent mutants reveals features of the conserved Eya domain. Genetics 155, 709-720.Cai, S., Cheng, X., Liu, Y., Lin, Z., Zeng, W., Yang, C., Liu, L., Chukwuebuka, O.A., and Li, W. (2018). EYA1 promotes tumor angiogenesis by activating the PI3K pathway in colorectal cancer. Exp Cell Res 367, 37-46.Cancer Genome Atlas Research, N., Brat, D.J., Verhaak, R.G., Aldape, K.D., Yung, W.K., Salama, S.R., Cooper, L.A., Rheinbay, E., Miller, C.R., Vitucci, M., et al. (2015). Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med 372, 2481-2498.Cancer Genome Atlas Research, N., Weinstein, J.N., Collisson, E.A., Mills, G.B., Shaw, K.R., Ozenberger, B.A., Ellrott, K., Shmulevich, I., Sander, C., and Stuart, J.M. (2013). The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113-1120.Castel, D., Philippe, C., Calmon, R., Le Dret, L., Truffaux, N., Boddaert, N., Pages, M., Taylor, K.R., Saulnier, P., Lacroix, L., et al. (2015). Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130, 815-827.Chang, C.Y., Pan, P.H., Wu, C.C., Liao, S.L., Chen, W.Y., Kuan, Y.H., Wang, W.Y., and Chen, C.J. (2021). Endoplasmic Reticulum Stress Contributes to Gefitinib-Induced Apoptosis in Glioma. Int J Mol Sci 22.Chen, G., Ning, B., and Shi, T. (2019). Single-Cell RNA-Seq Technologies and Related Computational Data Analysis. Front Genet 10, 317.Chen, R., Amoui, M., Zhang, Z., and Mardon, G. (1997). Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91, 893-903.Chen, W., Xia, T., Wang, D., Huang, B., Zhao, P., Wang, J., Qu, X., and Li, X. (2016a). Human astrocytes secrete IL-6 to promote glioma migration and invasion through upregulation of cytomembrane MMP14. Oncotarget 7, 62425-62438.Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., Jemal, A., Yu, X.Q., and He, J. (2016b). Cancer statistics in China, 2015. CA Cancer J Clin 66, 115-132.Choi, H.S., Kim, A.R., Kim, S.H., and Choi, B.Y. (2016). Identification of a novel truncation mutation of EYA4 in moderate degree hearing loss by targeted exome sequencing. Eur Arch Otorhinolaryngol 273, 1123-1129.Chu, C.W., Yang, M.C., Chou, C.H., Huang, W.S., Hsiao, B.X., Wang, Y.T., Chiou, S.J., Loh, J.K., and Hong, Y.R. (2018). GSK3betamediated Ser156 phosphorylation modulates a BH3like domain in BCL2L12 during TMZinduced apoptosis and autophagy in glioma cells. Int J Mol Med 42, 905-918.Chung, D.S., Shin, H.J., and Hong, Y.K. (2014). A new hope in immunotherapy for malignant gliomas: adoptive T cell transfer therapy. J Immunol Res 2014, 326545.Claes, A., Idema, A.J., and Wesseling, P. (2007). Diffuse glioma growth: a guerilla war. Acta Neuropathol 114, 443-458.Claus, E.B., Walsh, K.M., Wiencke, J.K., Molinaro, A.M., Wiemels, J.L., Schildkraut, J.M., Bondy, M.L., Berger, M., Jenkins, R., and Wrensch, M. (2015). Survival and low-grade glioma: the emergence of genetic information. Neurosurg Focus 38, E6.Cohen, A.L., Holmen, S.L., and Colman, H. (2013). IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep 13, 345.Cook, P.J., Ju, B.G., Telese, F., Wang, X., Glass, C.K., and Rosenfeld, M.G. (2009). Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature 458, 591-596.Davis, M.E. (2016). Glioblastoma: Overview of Disease and Treatment. Clin J Oncol Nurs 20, S2-8.Delgado-Martin, B., and Medina, M.A. (2020). Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment. Adv Sci (Weinh) 7, 1902971.Ding, H., Roncari, L., Shannon, P., Wu, X., Lau, N., Karaskova, J., Gutmann, D.H., Squire, J.A., Nagy, A., and Guha, A. (2001). Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res 61, 3826-3836.Dipro, S., Al-Otaibi, F., Alzahrani, A., Ulhaq, A., and Al Shail, E. (2012). Turcot syndrome: a synchronous clinical presentation of glioblastoma multiforme and adenocarcinoma of the colon. Case Rep Oncol Med 2012, 720273.Dufour, C., Cadusseau, J., Varlet, P., Surena, A.L., de Faria, G.P., Dias-Morais, A., Auger, N., Leonard, N., Daudigeos, E., Dantas-Barbosa, C., et al. (2009). Astrocytes reverted to a neural progenitor-like state with transforming growth factor alpha are sensitized to cancerous transformation. Stem Cells 27, 2373-2382.Eckel-Passow, J.E., Lachance, D.H., Molinaro, A.M., Walsh, K.M., Decker, P.A., Sicotte, H., Pekmezci, M., Rice, T., Kosel, M.L., Smirnov, I.V., et al. (2015). Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med 372, 2499-2508.Eisner, A., Pazyra-Murphy, M.F., Durresi, E., Zhou, P., Zhao, X., Chadwick, E.C., Xu, P.X., Hillman, R.T., Scott, M.P., Greenberg, M.E., et al. (2015). The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis. Dev Cell 33, 22-35.Eriksson, D., and Stigbrand, T. (2010). Radiation-induced cell death mechanisms. Tumour Biol 31, 363-372.Fan, X., Brass, L.F., Poncz, M., Spitz, F., Maire, P., and Manning, D.R. (2000). The alpha subunits of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins. J Biol Chem 275, 32129-32134.Farabaugh, S.M., Micalizzi, D.S., Jedlicka, P., Zhao, R., and Ford, H.L. (2012). Eya2 is required to mediate the pro-metastatic functions of Six1 via the induction of TGF-beta signaling, epithelial-mesenchymal transition, and cancer stem cell properties. Oncogene 31, 552-562.Ferrer, V.P., Moura Neto, V., and Mentlein, R. (2018). Glioma infiltration and extracellular matrix: key players and modulators. Glia 66, 1542-1565.Fruttiger, M., Karlsson, L., Hall, A.C., Abramsson, A., Calver, A.R., Bostrom, H., Willetts, K., Bertold, C.H., Heath, J.K., Betsholtz, C., et al. (1999). Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 126, 457-467.Gargini, R., Segura-Collar, B., and Sanchez-Gomez, P. (2020). Cellular Plasticity and Tumor Microenvironment in Gliomas: The Struggle to Hit a Moving Target. Cancers (Basel) 12.Ghaffari-Rafi, A., and Samandouras, G. (2020). Effect of Treatment Modalities on Progression-Free Survival and Overall Survival in Molecularly Subtyped World Health Organization Grade II Diffuse Gliomas: A Systematic Review. World Neurosurg 133, 366-380 e362.Gil-Gil, M.J., Mesia, C., Rey, M., and Bruna, J. (2013). Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol 7, 123-135.Griffin, C.A., Burger, P., Morsberger, L., Yonescu, R., Swierczynski, S., Weingart, J.D., and Murphy, K.M. (2006). Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol 65, 988-994.Haase, S., Garcia-Fabiani, M.B., Carney, S., Altshuler, D., Nunez, F.J., Mendez, F.M., Nunez, F., Lowenstein, P.R., and Castro, M.G. (2018). Mutant ATRX: uncovering a new therapeutic target for glioma. Expert Opin Ther Targets 22, 599-613.Han, S., Liu, Y., Cai, S.J., Qian, M., Ding, J., Larion, M., Gilbert, M.R., and Yang, C. (2020). IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer 122, 1580-1589.Han, X., Wang, R., Zhou, Y., Fei, L., Sun, H., Lai, S., Saadatpour, A., Zhou, Z., Chen, H., Ye, F., et al. (2018). Mapping the Mouse Cell Atlas by Microwell-Seq. Cell 173, 1307.Hao, X.Y., Cai, J.P., Liu, X., Chen, W., Hou, X., Chen, D., Lai, J.M., Liang, L.J., and Yin, X.Y. (2016). EYA4 gene functions as a prognostic marker and inhibits the growth of intrahepatic cholangiocarcinoma. Chin J Cancer 35, 70.Hartmann, C., Meyer, J., Balss, J., Capper, D., Mueller, W., Christians, A., Felsberg, J., Wolter, M., Mawrin, C., Wick, W., et al. (2009). Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118, 469-474.Hegde, R.S., Roychoudhury, K., and Pandey, R.N. (2020). The multi-functional eyes absent proteins. Crit Rev Biochem Mol Biol 55, 372-385.Heidenreich, B., and Kumar, R. (2017). TERT promoter mutations in telomere biology. Mutat Res Rev Mutat Res 771, 15-31.Hong, X., Sin, W.C., Harris, A.L., and Naus, C.C. (2015). Gap junctions modulate glioma invasion by direct transfer of microRNA. Oncotarget 6, 15566-15577.Hori, K., Sen, A., and Artavanis-Tsakonas, S. (2013). Notch signaling at a glance. J Cell Sci 126, 2135-2140.Hu, H., Mu, Q., Bao, Z., Chen, Y., Liu, Y., Chen, J., Wang, K., Wang, Z., Nam, Y., Jiang, B., et al. (2018). Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. Cell 175, 1665-1678 e1618.Hu, S., Mamedova, A., and Hegde, R.S. (2008). DNA-binding and regulation mechanisms of the SIX family of retinal determination proteins. Biochemistry 47, 3586-3594.Huang, J., Yu, J., Tu, L., Huang, N., Li, H., and Luo, Y. (2019). Isocitrate Dehydrogenase Mutations in Glioma: From Basic Discovery to Therapeutics Development. Front Oncol 9, 506.Ikeda, K., Watanabe, Y., Ohto, H., and Kawakami, K. (2002). Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol Cell Biol 22, 6759-6766.Jakel, S., and Dimou, L. (2017). Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation. Front Cell Neurosci 11, 24.Johung, T., and Monje, M. (2017). Neuronal activity in the glioma microenvironment. Curr Opin Neurobiol 47, 156-161.Jung, S.K., Jeong, D.G., Chung, S.J., Kim, J.H., Park, B.C., Tonks, N.K., Ryu, S.E., and Kim, S.J. (2010). Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor. FASEB J 24, 560-569.Karousou, E., Misra, S., Ghatak, S., Dobra, K., Gotte, M., Vigetti, D., Passi, A., Karamanos, N.K., and Skandalis, S.S. (2017). Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer. Matrix Biol 59, 3-22.Kaur, H., Lachance, D.H., Ryan, C.S., Sheen, Y.H., Seol, H.Y., Wi, C.I., Sohn, S., King, K.S., Ryu, E., and Juhn, Y. (2019). Asthma and risk of glioma: a population-based case-control study. BMJ Open 9, e025746.Kim, J., She, C., Potez, M., Huang, P., Wu, Q., Prager, B.C., Qiu, Z., Bao, S., Rich, J.N., and Liu, J.K.C. (2021). Phage display targeting identifies EYA1 as a regulator of glioblastoma stem cell maintenance and proliferation. Stem Cells 39, 853-865.Komohara, Y., Ohnishi, K., Kuratsu, J., and Takeya, M. (2008). Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol 216, 15-24.Kong, D., Li, A., Liu, Y., Cui, Q., Wang, K., Zhang, D., Tang, J., Du, Y., Liu, Z., Wu, G., et al. (2019a). SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1. Front Oncol 9, 1450.Kong, D., Ma, W., Zhang, D., Cui, Q., Wang, K., Tang, J., Liu, Z., and Wu, G. (2019b). EYA1 promotes cell migration and tumor metastasis in hepatocellular carcinoma. Am J Transl Res 11, 2328-2338.Krishnan, N., Jeong, D.G., Jung, S.K., Ryu, S.E., Xiao, A., Allis, C.D., Kim, S.J., and Tonks, N.K. (2009). Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent. J Biol Chem 284, 16066-16070.Krueger, A.B., Dehdashti, S.J., Southall, N., Marugan, J.J., Ferrer, M., Li, X., Ford, H.L., Zheng, W., and Zhao, R. (2013). Identification of a selective small-molecule inhibitor series targeting the eyes absent 2 (Eya2) phosphatase activity. J Biomol Screen 18, 85-96.Krueger, A.B., Drasin, D.J., Lea, W.A., Patrick, A.N., Patnaik, S., Backos, D.S., Matheson, C.J., Hu, X., Barnaeva, E., Holliday, M.J., et al. (2014). Allosteric inhibitors of the Eya2 phosphatase are selective and inhibit Eya2-mediated cell migration. J Biol Chem 289, 16349-16361.Kumthekar, P., Ko, C.H., Paunesku, T., Dixit, K., Sonabend, A.M., Bloch, O., Tate, M., Schwartz, M., Zuckerman, L., Lezon, R., et al. (2021). A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma. Sci Transl Med 13.Kwon, C.H., Zhao, D., Chen, J., Alcantara, S., Li, Y., Burns, D.K., Mason, R.P., Lee, E.Y., Wu, H., and Parada, L.F. (2008). Pten haploinsufficiency accelerates formation of high-grade astrocytomas. Cancer Res 68, 3286-3294.Landgraf, K., Bollig, F., Trowe, M.O., Besenbeck, B., Ebert, C., Kruspe, D., Kispert, A., Hanel, F., and Englert, C. (2010). Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in craniofacial development. Mol Cell Biol 30, 5764-5775.Lapointe, S., Perry, A., and Butowski, N.A. (2018). Primary brain tumours in adults. Lancet 392, 432-446.Lawn, S., Krishna, N., Pisklakova, A., Qu, X., Fenstermacher, D.A., Fournier, M., Vrionis, F.D., Tran, N., Chan, J.A., Kenchappa, R.S., et al. (2015). Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells. J Biol Chem 290, 3814-3824.Laws, E.R., Jr., and Shaffrey, M.E. (1999). The inherent invasiveness of cerebral gliomas: implications for clinical management. Int J Dev Neurosci 17, 413-420.Li, J., Rodriguez, Y., Cheng, C., Zeng, L., Wong, E.Y.M., Xu, C.Y., Zhou, M.M., and Xu, P.X. (2017a). EYA1's Conformation Specificity in Dephosphorylating Phosphothreonine in Myc and Its Activity on Myc Stabilization in Breast Cancer. Mol Cell Biol 37.Li, Z., Qiu, R., Qiu, X., and Tian, T. (2017b). EYA2 promotes lung cancer cell proliferation by downregulating the expression of PTEN. Oncotarget 8, 110837-110848.Li, Z., Qiu, R., Qiu, X., and Tian, T. (2018). EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma. Cell Physiol Biochem 49, 1856-1869.Liu, C., Sage, J.C., Miller, M.R., Verhaak, R.G., Hippenmeyer, S., Vogel, H., Foreman, O., Bronson, R.T., Nishiyama, A., Luo, L., et al. (2011). Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell 146, 209-221.Liu, X., Sano, T., Guan, Y., Nagata, S., Hoffmann, J.A., and Fukuyama, H. (2012). Drosophila EYA regulates the immune response against DNA through an evolutionarily conserved threonine phosphatase motif. PLoS One 7, e42725.Liu, Z., Zhao, L., and Song, Y. (2019). Eya2 Is Overexpressed in Human Prostate Cancer and Regulates Docetaxel Sensitivity and Mitochondrial Membrane Potential through AKT/Bcl-2 Signaling. Biomed Res Int 2019, 3808432.Lobbous, M., Bernstock, J.D., Coffee, E., Friedman, G.K., Metrock, L.K., Chagoya, G., Elsayed, G., Nakano, I., Hackney, J.R., Korf, B.R., et al. (2020). An Update on Neurofibromatosis Type 1-Associated Gliomas. Cancers (Basel) 12.Louis, D.N., Perry, A., Wesseling, P., Brat, D.J., Cree, I.A., Figarella-Branger, D., Hawkins, C., Ng, H.K., Pfister, S.M., Reifenberger, G., et al. (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 23, 1231-1251.Luo, M., Li, Y., Shi, X., Yang, W., Zhou, F., Sun, N., and He, J. (2018). Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Cancer Sci 109, 1811-1824.Maeda, N. (2015). Proteoglycans and neuronal migration in the cerebral cortex during development and disease. Front Neurosci 9, 98.Manley, P.W., Cowan-Jacob, S.W., Buchdunger, E., Fabbro, D., Fendrich, G., Furet, P., Meyer, T., and Zimmermann, J. (2002). Imatinib: a selective tyrosine kinase inhibitor. Eur J Cancer 38 Suppl 5, S19-27.Martinelli, E., De Palma, R., Orditura, M., De Vita, F., and Ciardiello, F. (2009). Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol 158, 1-9.Massara, M., Persico, P., Bonavita, O., Mollica Poeta, V., Locati, M., Simonelli, M., and Bonecchi, R. (2017). Neutrophils in Gliomas. Front Immunol 8, 1349.Mentel, M., Ionescu, A.E., Puscalau-Girtu, I., Helm, M.S., Badea, R.A., Rizzoli, S.O., and Szedlacsek, S.E. (2018). WDR1 is a novel EYA3 substrate and its dephosphorylation induces modifications of the cellular actin cytoskeleton. Sci Rep 8, 2910.Merk, D.J., Zhou, P., Cohen, S.M., Pazyra-Murphy, M.F., Hwang, G.H., Rehm, K.J., Alfaro, J., Reid, C.M., Zhao, X., Park, E., et al. (2020). The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors. Dev Neurosci 42, 170-186.Miller, K.D., Ostrom, Q.T., Kruchko, C., Patil, N., Tihan, T., Cioffi, G., Fuchs, H.E., Waite, K.A., Jemal, A., Siegel, R.L., et al. (2021). Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin 71, 381-406.Miller, S.J., Lan, Z.D., Hardiman, A., Wu, J., Kordich, J.J., Patmore, D.M., Hegde, R.S., Cripe, T.P., Cancelas, J.A., Collins, M.H., et al. (2010). Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene 29, 368-379.Mo, S.J., Liu, X., Hao, X.Y., Chen, W., Zhang, K.S., Cai, J.P., Lai, J.M., Liang, L.J., and Yin, X.Y. (2016). EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through beta-catenin/ID2 pathway. Cancer Lett 380, 403-412.Montalto, F.I., and De Amicis, F. (2020). Cyclin D1 in Cancer: A Molecular Connection for Cell Cycle Control, Adhesion and Invasion in Tumor and Stroma. Cells 9.Nazarenko, I., Hede, S.M., He, X., Hedren, A., Thompson, J., Lindstrom, M.S., and Nister, M. (2012). PDGF and PDGF receptors in glioma. Ups J Med Sci 117, 99-112.Nikpour, P., Emadi-Baygi, M., Emadi-Andani, E., and Rahmati, S. (2014). EYA1 expression in gastric carcinoma and its association with clinicopathological characteristics: a pilot study. Med Oncol 31, 955.Norden, A.D., and Wen, P.Y. (2006). Glioma therapy in adults. Neurologist 12, 279-292.Ohgaki, H., and Kleihues, P. (2005). Epidemiology and etiology of gliomas. Acta Neuropathol 109, 93-108.Okabe, Y., Sano, T., and Nagata, S. (2009). Regulation of the innate immune response by threonine-phosphatase of Eyes absent. Nature 460, 520-524.Oprita, A., Baloi, S.C., Staicu, G.A., Alexandru, O., Tache, D.E., Danoiu, S., Micu, E.S., and Sevastre, A.S. (2021). Updated Insights on EGFR Signaling Pathways in Glioma. Int J Mol Sci 22.Ostrom, Q.T., Cioffi, G., Gittleman, H., Patil, N., Waite, K., Kruchko, C., and Barnholtz-Sloan, J.S. (2019). CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol 21, v1-v100.Park, H., Jung, S.K., Yu, K.R., Kim, J.H., Kim, Y.S., Ko, J.H., Park, B.C., and Kim, S.J. (2011). Structure-based virtual screening approach to the discovery of novel inhibitors of eyes absent 2 phosphatase with various metal chelating moieties. Chem Biol Drug Des 78, 642-650.Park, H., Ryu, S.E., and Kim, S.J. (2012). Structure-based de novo design of Eya2 phosphatase inhibitors. J Mol Graph Model 38, 382-388.Parsons, D.W., Jones, S., Zhang, X., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.M., Gallia, G.L., et al. (2008). An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807-1812.Patrick, A.N., Cabrera, J.H., Smith, A.L., Chen, X.S., Ford, H.L., and Zhao, R. (2013). Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome. Nat Struct Mol Biol 20, 447-453.Pierce, G.B. (1983). The cancer cell and its control by the embryo. Rous-Whipple Award lecture. Am J Pathol 113, 117-124.Pines, G., Kostler, W.J., and Yarden, Y. (2010). Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy. FEBS Lett 584, 2699-2706.Powter, B., Jeffreys, S.A., Sareen, H., Cooper, A., Brungs, D., Po, J., Roberts, T., Koh, E.S., Scott, K.F., Sajinovic, M., et al. (2021). Human TERT promoter mutations as a prognostic biomarker in glioma. J Cancer Res Clin Oncol 147, 1007-1017.Prasad, G., and Haas-Kogan, D.A. (2009). Radiation-induced gliomas. Expert Rev Neurother 9, 1511-1517.Qie, S., and Diehl, J.A. (2016). Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med (Berl) 94, 1313-1326.Quail, D.F., and Joyce, J.A. (2017). The Microenvironmental Landscape of Brain Tumors. Cancer Cell 31, 326-341.Rahbar, A., Cederarv, M., Wolmer-Solberg, N., Tammik, C., Stragliotto, G., Peredo, I., Fornara, O., Xu, X., Dzabic, M., Taher, C., et al. (2016). Enhanced neutrophil activity is associated with shorter time to tumor progression in glioblastoma patients. Oncoimmunology 5, e1075693.Raizer, J.J. (2005). HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme. J Neurooncol 74, 77-86.Rajabi, M., and Mousa, S.A. (2017). The Role of Angiogenesis in Cancer Treatment. Biomedicines 5.Rayapureddi, J.P., Kattamuri, C., Steinmetz, B.D., Frankfort, B.J., Ostrin, E.J., Mardon, G., and Hegde, R.S. (2003). Eyes absent represents a class of protein tyrosine phosphatases. Nature 426, 295-298.Rebay, I. (2015). Multiple Functions of the Eya Phosphotyrosine Phosphatase. Mol Cell Biol 36, 668-677.Reifenberger, G., Wirsching, H.G., Knobbe-Thomsen, C.B., and Weller, M. (2017). Advances in the molecular genetics of gliomas - implications for classification and therapy. Nat Rev Clin Oncol 14, 434-452.Rickard, S., Parker, M., van't Hoff, W., Barnicoat, A., Russell-Eggitt, I., Winter, R.M., and Bitner-Glindzicz, M. (2001). Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM. Hum Genet 108, 398-403.Roberts, W.G., Whalen, P.M., Soderstrom, E., Moraski, G., Lyssikatos, J.P., Wang, H.F., Cooper, B., Baker, D.A., Savage, D., Dalvie, D., et al. (2005). Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res 65, 957-966.Robin, T.P., Smith, A., McKinsey, E., Reaves, L., Jedlicka, P., and Ford, H.L. (2012). EWS/FLI1 regulates EYA3 in Ewing sarcoma via modulation of miRNA-708, resulting in increased cell survival and chemoresistance. Mol Cancer Res 10, 1098-1108.Roychoudhury, K., and Hegde, R.S. (2021). The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases. Int J Mol Sci 22.Ruiz-Garcia, H., Alvarado-Estrada, K., Schiapparelli, P., Quinones-Hinojosa, A., and Trifiletti, D.M. (2020). Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment. Front Cell Neurosci 14, 558381.Sano, T., and Nagata, S. (2011). Characterization of the threonine-phosphatase of mouse eyes absent 3. FEBS Lett 585, 2714-2719.Santos, P.M., and Butterfield, L.H. (2018). Dendritic Cell-Based Cancer Vaccines. J Immunol 200, 443-449.Schreck, K.C., Grossman, S.A., and Pratilas, C.A. (2019). BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors. Cancers (Basel) 11.Schwartzentruber, J., Korshunov, A., Liu, X.Y., Jones, D.T., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A.M., Quang, D.A., Tonjes, M., et al. (2012). Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226-231.Sell, S., Nicolini, A., Ferrari, P., and Biava, P.M. (2016). Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy. Curr Drug Targets 17, 1103-1110.Sharif, A., Legendre, P., Prevot, V., Allet, C., Romao, L., Studler, J.M., Chneiweiss, H., and Junier, M.P. (2007). Transforming growth factor alpha promotes sequential conversion of mature astrocytes into neural progenitors and stem cells. Oncogene 26, 2695-2706.Shimasaki, N., Watanabe, K., Hara, M., and Kosaki, K. (2004). EYA1 mutation in a newborn female presenting with cardiofacial syndrome. Pediatr Cardiol 25, 411-413.Shoshan, Y., Nishiyama, A., Chang, A., Mork, S., Barnett, G.H., Cowell, J.K., Trapp, B.D., and Staugaitis, S.M. (1999). Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors. Proc Natl Acad Sci U S A 96, 10361-10366.Siegel, R.L., Miller, K.D., Fuchs, H.E., and Jemal, A. (2022). Cancer statistics, 2022. CA Cancer J Clin 72, 7-33.Siegel, R.L., Miller, K.D., and Jemal, A. (2020). Cancer statistics, 2020. CA Cancer J Clin 70, 7-30.Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., and Dirks, P.B. (2004). Identification of human brain tumour initiating cells. Nature 432, 396-401.Sloan, E.A., Hilz, S., Gupta, R., Cadwell, C., Ramani, B., Hofmann, J., Kline, C.N., Banerjee, A., Reddy, A., Oberheim Bush, N.A., et al. (2020). Gliomas arising in the setting of Li-Fraumeni syndrome stratify into two molecular subgroups with divergent clinicopathologic features. Acta Neuropathol 139, 953-957.Soni, U.K., Roychoudhury, K., and Hegde, R.S. (2021). The Eyes Absent proteins in development and in developmental disorders. Biochem Soc Trans 49, 1397-1408.Stegh, A.H., Brennan, C., Mahoney, J.A., Forloney, K.L., Jenq, H.T., Luciano, J.P., Protopopov, A., Chin, L., and Depinho, R.A. (2010). Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor. Genes Dev 24, 2194-2204.Stegh, A.H., Kesari, S., Mahoney, J.E., Jenq, H.T., Forloney, K.L., Protopopov, A., Louis, D.N., Chin, L., and DePinho, R.A. (2008). Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma. Proc Natl Acad Sci U S A 105, 10703-10708.Sun, D., Wang, J., Han, Y., Dong, X., Ge, J., Zheng, R., Shi, X., Wang, B., Li, Z., Ren, P., et al. (2021). TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res 49, D1420-D1430.Suzuki, S.O., Mizoguchi, M., and Iwaki, T. (1997). Detection of SV40 T antigen genome in human gliomas. Brain Tumor Pathol 14, 125-129.Tadjuidje, E., Wang, T.S., Pandey, R.N., Sumanas, S., Lang, R.A., and Hegde, R.S. (2012). The EYA tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromarone. PLoS One 7, e34806.Towle, R., Truong, D., and Garnis, C. (2016). Epigenetic mediated silencing of EYA4 contributes to tumorigenesis in oral dysplastic cells. Genes Chromosomes Cancer 55, 568-576.Uhrbom, L., Kastemar, M., Johansson, F.K., Westermark, B., and Holland, E.C. (2005). Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis. Cancer Res 65, 2065-2069.Vartuli, R.L., Zhou, H., Zhang, L., Powers, R.K., Klarquist, J., Rudra, P., Vincent, M.Y., Ghosh, D., Costello, J.C., Kedl, R.M., et al. (2018). Eya3 promotes breast tumor-associated immune suppression via threonine phosphatase-mediated PD-L1 upregulation. J Clin Invest 128, 2535-2550.Venkatesh, H.S., Johung, T.B., Caretti, V., Noll, A., Tang, Y., Nagaraja, S., Gibson, E.M., Mount, C.W., Polepalli, J., Mitra, S.S., et al. (2015). Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion. Cell 161, 803-816.Verhaak, R.G., Hoadley, K.A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M.D., Miller, C.R., Ding, L., Golub, T., Mesirov, J.P., et al. (2010). Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98-110.Verkhratsky, A., Matteoli, M., Parpura, V., Mothet, J.P., and Zorec, R. (2016). Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion. EMBO J 35, 239-257.Vilchez, R.A., and Butel, J.S. (2004). Emergent human pathogen simian virus 40 and its role in cancer. Clin Microbiol Rev 17, 495-508, table of contents.Vincent, A., Hong, S.M., Hu, C., Omura, N., Young, A., Kim, H., Yu, J., Knight, S., Ayars, M., Griffith, M., et al. (2014). Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth. Oncotarget 5, 2575-2587.Wang, F., Yan, Z., Lv, J., Xin, J., Dang, Y., Sun, X., An, Y., Qi, Y., Jiang, Q., Zhu, W., et al. (2019a). Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations. Neoplasia 21, 571-581.Wang, G., Xu, S., Cao, C., Dong, J., Chu, Y., He, G., and Xu, Z. (2016). Evidence from a large-scale meta-analysis indicates eczema reduces the incidence of glioma. Oncotarget 7, 62598-62606.Wang, Y., Luo, W., and Wang, Y. (2019b). PARP-1 and its associated nucleases in DNA damage response. DNA Repair (Amst) 81, 102651.Weissenberger, J., Steinbach, J.P., Malin, G., Spada, S., Rulicke, T., and Aguzzi, A. (1997). Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene 14, 2005-2013.Weller, M., Pfister, S.M., Wick, W., Hegi, M.E., Reifenberger, G., and Stupp, R. (2013). Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol 14, e370-379.Wen, Z., Liang, C., Pan, Q., and Wang, Y. (2017). Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling. Int J Mol Med 40, 1315-1322.Weng, J., Luo, J., Cheng, X., Jin, C., Zhou, X., Qu, J., Tu, L., Ai, D., Li, D., Wang, J., et al. (2008). Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2. Proc Natl Acad Sci U S A 105, 6081-6086.Wu, K., Li, Z., Cai, S., Tian, L., Chen, K., Wang, J., Hu, J., Sun, Y., Li, X., Ertel, A., et al. (2013). EYA1 phosphatase function is essential to drive breast cancer cell proliferation through cyclin D1. Cancer Res 73, 4488-4499.Xiao, A., Li, H., Shechter, D., Ahn, S.H., Fabrizio, L.A., Erdjument-Bromage, H., Ishibe-Murakami, S., Wang, B., Tempst, P., Hofmann, K., et al. (2009). WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 457, 57-62.Xiao, A., Wu, H., Pandolfi, P.P., Louis, D.N., and Van Dyke, T. (2002). Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell 1, 157-168.Xie, Y., Bergstrom, T., Jiang, Y., Johansson, P., Marinescu, V.D., Lindberg, N., Segerman, A., Wicher, G., Niklasson, M., Baskaran, S., et al. (2015). The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes. EBioMedicine 2, 1351-1363.Xu, H., Jiao, Y., Yi, M., Zhao, W., and Wu, K. (2019). EYA2 Correlates With Clinico-Pathological Features of Breast Cancer, Promotes Tumor Proliferation, and Predicts Poor Survival. Front Oncol 9, 26.Xu, J., Wong, E.Y., Cheng, C., Li, J., Sharkar, M.T., Xu, C.Y., Chen, B., Sun, J., Jing, D., and Xu, P.X. (2014). Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis. Dev Cell 31, 434-447.Xu, P.X., Cheng, J., Epstein, J.A., and Maas, R.L. (1997). Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function. Proc Natl Acad Sci U S A 94, 11974-11979.Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.H., Ito, S., Yang, C., Wang, P., Xiao, M.T., et al. (2011). Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19, 17-30.Yamanaka, R., Hayano, A., and Kanayama, T. (2018). Radiation-induced gliomas: a comprehensive review and meta-analysis. Neurosurg Rev 41, 719-731.Yang, H., Ye, D., Guan, K.L., and Xiong, Y. (2012). IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res 18, 5562-5571.Yang, J., Hong, Y., Wang, W., Wu, W., Chi, Y., Zong, H., Kong, X., Wei, Y., Yun, X., Cheng, C., et al. (2009). HSP70 protects BCL2L12 and BCL2L12A from N-terminal ubiquitination-mediated proteasomal degradation. FEBS Lett 583, 1409-1414.Yang, M.C., Loh, J.K., Li, Y.Y., Huang, W.S., Chou, C.H., Cheng, J.T., Wang, Y.T., Lieu, A.S., Howng, S.L., Hong, Y.R., et al. (2015). Bcl2L12 with a BH3-like domain in regulating apoptosis and TMZ-induced autophagy: a prospective combination of ABT-737 and TMZ for treating glioma. Int J Oncol 46, 1304-1316.Yin, J., Valin, K.L., Dixon, M.L., and Leavenworth, J.W. (2017). The Role of Microglia and Macrophages in CNS Homeostasis, Autoimmunity, and Cancer. J Immunol Res 2017, 5150678.Young, R.M., Jamshidi, A., Davis, G., and Sherman, J.H. (2015). Current trends in the surgical management and treatment of adult glioblastoma. Ann Transl Med 3, 121.Yu, M.W., and Quail, D.F. (2021). Immunotherapy for Glioblastoma: Current Progress and Challenges. Front Immunol 12, 676301.Yuan, B., Cheng, L., Chiang, H.C., Xu, X., Han, Y., Su, H., Wang, L., Zhang, B., Lin, J., Li, X., et al. (2014). A phosphotyrosine switch determines the antitumor activity of ERbeta. J Clin Invest 124, 3378-3390.Zhang, H., Wang, L., Wong, E.Y.M., Tsang, S.L., Xu, P.X., Lendahl, U., and Sham, M.H. (2017). An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis. Elife 6.Zhang, L., Yang, N., Huang, J., Buckanovich, R.J., Liang, S., Barchetti, A., Vezzani, C., O'Brien-Jenkins, A., Wang, J., Ward, M.R., et al. (2005). Transcriptional coactivator Drosophila eyes absent homologue 2 is up-regulated in epithelial ovarian cancer and promotes tumor growth. Cancer Res 65, 925-932.Zhang, L., Zhou, H., Li, X., Vartuli, R.L., Rowse, M., Xing, Y., Rudra, P., Ghosh, D., Zhao, R., and Ford, H.L. (2018a). Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression. Nat Commun 9, 1047.Zhang, Y., Dube, C., Gibert, M., Jr., Cruickshanks, N., Wang, B., Coughlan, M., Yang, Y., Setiady, I., Deveau, C., Saoud, K., et al. (2018b). The p53 Pathway in Glioblastoma. Cancers (Basel) 10.Zheng, J., Cao, F., Huang, X., Ramen, K., Xu, X., Zhu, Y., Chang, W., Shan, Y., and Guo, A. (2018). Eyes absent homologue 2 predicts a favorable prognosis in colorectal cancer. Onco Targets Ther 11, 4661-4671.Zhu, G., Xie, J., Kong, W., Xie, J., Li, Y., Du, L., Zheng, Q., Sun, L., Guan, M., Li, H., et al. (2020). Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation. Cell 183, 490-502 e418.Zhu, X.X., Li, J.H., Cai, J.P., Hou, X., Huang, C.S., Huang, X.T., Wang, J.Q., Li, S.J., Xu, Q.C., and Yin, X.Y. (2019). EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating beta-catenin at Ser552. Cancer Sci 110, 3110-3121.Zhu, Y., Guignard, F., Zhao, D., Liu, L., Burns, D.K., Mason, R.P., Messing, A., and Parada, L.F. (2005). Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8, 119-130.Zou, D., Erickson, C., Kim, E.H., Jin, D., Fritzsch, B., and Xu, P.X. (2008). Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear. Hum Mol Genet 17, 3340-3356.Zou, H., Osborn, N.K., Harrington, J.J., Klatt, K.K., Molina, J.R., Burgart, L.J., and Ahlquist, D.A. (2005). Frequent methylation of eyes absent 4 gene in Barrett's esophagus and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev 14, 830-834.

Data Source
Document TypeThesis
DepartmentDepartment of Biology
Recommended Citation
GB/T 7714
Wei TZ. Functional Study of EYA1 in Glioma Formation and Progression[D]. 香港. 香港大学,2022.
Files in This Item:
File Name/Size DocType Version Access License
11850022-魏天资-生物系.pdf(5023KB) Restricted Access--Fulltext Requests
Related Services
Recommend this item
Usage statistics
Export to Endnote
Export to Excel
Export to Csv
Altmetrics Score
Google Scholar
Similar articles in Google Scholar
[魏天资]'s Articles
Baidu Scholar
Similar articles in Baidu Scholar
[魏天资]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[魏天资]'s Articles
Terms of Use
No data!
Social Bookmark/Share
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.