Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

1 Scopus Citations
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Author(s)

  • Yingying Lu
  • Yunjiao He
  • Jingting Yu
  • Wenjie Wei
  • Chang Chen
  • Rui Wang
  • Liangren Zhang
  • Minh T. N. Le
  • William C. Cho
  • Hongmin Zhang

Detail(s)

Original languageEnglish
Pages (from-to)1775–1791
Journal / PublicationOncogene
Volume40
Issue number10
Online published9 Feb 2021
Publication statusPublished - 10 Mar 2021

Abstract

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 Zβ (CapZβ) 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 CapZβ to inhibit endosomal trafficking and metastasis.

Citation Format(s)

Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. / Ye, Zuodong; Wang, Dawei; Lu, Yingying; He, Yunjiao; Yu, Jingting; Wei, Wenjie; Chen, Chang; Wang, Rui; Zhang, Liang; Zhang, Liangren; Le, Minh T. N.; Cho, William C.; Yang, Mengsu; Zhang, Hongmin; Yue, Jianbo.

In: Oncogene, Vol. 40, No. 10, 10.03.2021, p. 1775–1791.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review