Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZ beta

Ye, Zuodong1,2; Wang, Dawei1,2; Lu, Yingying1,2; He, Yunjiao3,4; Yu, Jingting1; Wei, Wenjie5; Chen, Chang6; Wang, Rui1,2; Zhang, Liang1,2; Zhang, Liangren6; Le, Minh T. N.7; Cho, William C.8; Yang, Mengsu1,2; Zhang, Hongmin3,4; Yue, Jianbo1,2,9

2021-03-10

10.1038/s41388-021-01662-3

ONCOGENE   影响因子和分区

0950-9232

1476-5594

Metastasis is the fundamental cause of cancer mortality, but there are still very few anti-metastatic drugs available. Endosomal trafficking has been implicated in tumor metastasis, and we have previously found that small chemical vacuolin-1 (V1) potently inhibits autophagosome-lysosome fusion and general endosomal-lysosomal degradation. Here, we assessed the anti-metastatic activity of V1 both in vitro and in vivo. V1 significantly inhibits colony formation, migration, and invasion of various cancer cells in vitro. It also compromises the assembly-disassembly dynamics of focal adhesions (FAs) by inhibiting the recycling and degradation of integrins. In various experimental or transgenic mouse models, V1 significantly suppresses the metastasis and/or tumor growth of breast cancer or melanoma. We further identified capping protein Z beta (CapZ beta) as a V1 binding protein and showed that it is required for the V1-mediated inhibition of migration and metastasis of cancer cells. Collectively, our results indicate that V1 targets CapZ beta to inhibit endosomal trafficking and metastasis.

SCI

英语

其他

Hong Kong Research Grant Council (RGC)[11101717,11103620] ; NSFC[21778045,32070702,31670753,31501116] ; Guangdong Science and Technology Program[2017B030301018] ; Shenzhen Science and Technology Innovation Committee["JCYJ201602291652 35739","JCYJ20170413141331470","JCYJ20160608140912962","SYS20140509142721429"] ; Sichuan Provincial Science and Technology Research Grant[2019YJ0633]

Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity

Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity

WOS:000616489100007

SPRINGERNATURE

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.City Univ Hong Kong, Shenzhen Res Inst, Shenzhen, Peoples R China
2.City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China
3.Southern Univ Sci & Technol, Dept Biol, Guangdong Prov Key Lab Cell Microenvironm & Dis R, Shenzhen 518055, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Key Lab Cell Microenvironm, Shenzhen 518055, Peoples R China
5.South Univ Sci & Technol China, Res Core Facil, Shenzhen 518052, Peoples R China
6.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
7.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore
8.Queen Elizabeth Hosp, Dept Clin Oncol, 30 Gascoigne Rd, Hong Kong, Peoples R China
9.City Univ Hong Kong, Chengdu Res Inst, Chengdu, Peoples R China

Ye, Zuodong,Wang, Dawei,Lu, Yingying,et al. Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZ beta[J]. ONCOGENE,2021,40(10).

Ye, Zuodong.,Wang, Dawei.,Lu, Yingying.,He, Yunjiao.,Yu, Jingting.,...&Yue, Jianbo.(2021).Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZ beta.ONCOGENE,40(10).

Ye, Zuodong,et al."Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZ beta".ONCOGENE 40.10(2021).