| First Author | Ye Z | Year | 2021 |
| Journal | Oncogene | Volume | 40 |
| Issue | 10 | Pages | 1775-1791 |
| PubMed ID | 33564074 | Mgi Jnum | J:303961 |
| Mgi Id | MGI:6514586 | Doi | 10.1038/s41388-021-01662-3 |
| Citation | Ye Z, et al. (2021) Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZbeta. Oncogene 40(10):1775-1791 |
| abstractText | 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 Zbeta (CapZbeta) 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 CapZbeta to inhibit endosomal trafficking and metastasis. |
