Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3

Liu, Zihao1,2,6; Shi, Yu1,2; Lv, Li2,5; Chen, Jianing1,2; Jiang, WenG3; Li, Jun4; Lin, Qun1,2; Fang, Xiaolin1,2; Gao, Jingbo1,2; Liu, Yujie1,2; Liu, Qiang1,2; Xu, Xiaoding2; Song, Erwei1,2; Gong, Chang1,2

2022-10-01

10.1002/advs.202204649

ADVANCED SCIENCE   Impact Factor & Quartile

2198-3844

Most cancer-related deaths are a result of metastasis. The development of small molecular inhibitors reversing cancer metastasis represents a promising therapeutic opportunity for cancer patients. This pan-cancer analysis identifies oncogenic roles of membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3), which is crucial for cancer metastasis. Small molecules targeting PITPNM3 must be explored further. Here, PITPNM3-selective small molecular inhibitors are reported. These compounds exhibit target-specific inhibition of PITPNM3 signaling, thereby reducing metastasis of breast cancer cells. Besides, by using nanoparticle-based delivery systems, these PITPNM3-selective compounds loaded nanoparticles significantly repress metastasis of breast cancer in mouse xenograft models and organoid models. Notably, the results establish an important metastatic-promoting role for PITPNM3 and offer PITPNM3 inhibition as a therapeutic strategy in metastatic breast cancer.

metastasis pan-cancer analysis PITPNM3 small molecular inhibitors

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English

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Natural Science Foundation of China["81621004","92159303","81720108029","81930081","91940305","81872139","82072907"] ; Beijing Xisike Clinical Oncology Research Foundation["Y-Roche2019/2-0078","Y-pierrefabre202102-0107"] ; Technology Development Program of Guangdong province[2021A0505030082] ; Guangdong Science and Technology Department["2020B1212060018","2020B1212030004"] ; Project of The Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation[2020B1212060018] ; Department of Natural Resources of Guangdong Province[GDNRC[2021]51] ; Bureau of Science and Technology of Guangzhou[20212200003] ; Program for Guangdong Introducing Innovative and Enterpreneurial Teams[2019BT02Y198] ; Clinical Innovation Research Program of Bioland Laboratory[2018GZR0201004]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000871902400001

WILEY

Web of Science

1.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Peoples R China
2.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China
3.Cardiff Univ, Sch Med, Cardiff China Med Res Collaborat, Heath Pk, Cardiff CF14 4XN, Wales
4.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biochem, Guangzhou 510080, Peoples R China
5.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pharm, Guangzhou 510120, Peoples R China
6.Southern Univ Sci & Technol, Affiliated Hosp 1, Jinan Univ, Clin Med Coll 2,Dept Breast & Thyroid Surg,Shenzh, Shenzhen 518020, Peoples R China

Liu, Zihao,Shi, Yu,Lv, Li,et al. Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3[J]. ADVANCED SCIENCE,2022.

Liu, Zihao.,Shi, Yu.,Lv, Li.,Chen, Jianing.,Jiang, WenG.,...&Gong, Chang.(2022).Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3.ADVANCED SCIENCE.

Liu, Zihao,et al."Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3".ADVANCED SCIENCE (2022).