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Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ.

Publication ,  Journal Article
Ye, Z; Wang, D; Lu, Y; He, Y; Yu, J; Wei, W; Chen, C; Wang, R; Zhang, L; Zhang, L; Le, MTN; Cho, WC; Yang, M; Zhang, H; Yue, J
Published in: Oncogene
March 2021

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.

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Published In

Oncogene

DOI

EISSN

1476-5594

ISSN

0950-9232

Publication Date

March 2021

Volume

40

Issue

10

Start / End Page

1775 / 1791

Related Subject Headings

  • Protein Binding
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Mice, Transgenic
  • Mice
  • Lysosomes
  • Integrins
  • Humans
  • Heterocyclic Compounds, 4 or More Rings
  • Gene Expression Regulation, Neoplastic
 

Citation

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Ye, Z., Wang, D., Lu, Y., He, Y., Yu, J., Wei, W., … Yue, J. (2021). Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. Oncogene, 40(10), 1775–1791. https://doi.org/10.1038/s41388-021-01662-3
Ye, Zuodong, Dawei Wang, Yingying Lu, Yunjiao He, Jingting Yu, Wenjie Wei, Chang Chen, et al. “Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ.Oncogene 40, no. 10 (March 2021): 1775–91. https://doi.org/10.1038/s41388-021-01662-3.
Ye Z, Wang D, Lu Y, He Y, Yu J, Wei W, et al. Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. Oncogene. 2021 Mar;40(10):1775–91.
Ye, Zuodong, et al. “Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ.Oncogene, vol. 40, no. 10, Mar. 2021, pp. 1775–91. Epmc, doi:10.1038/s41388-021-01662-3.
Ye Z, Wang D, Lu Y, He Y, Yu J, Wei W, Chen C, Wang R, Zhang L, Le MTN, Cho WC, Yang M, Zhang H, Yue J. Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZβ. Oncogene. 2021 Mar;40(10):1775–1791.

Published In

Oncogene

DOI

EISSN

1476-5594

ISSN

0950-9232

Publication Date

March 2021

Volume

40

Issue

10

Start / End Page

1775 / 1791

Related Subject Headings

  • Protein Binding
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Mice, Transgenic
  • Mice
  • Lysosomes
  • Integrins
  • Humans
  • Heterocyclic Compounds, 4 or More Rings
  • Gene Expression Regulation, Neoplastic