Liver metastases still remain a major cause of colorectal cancer (CRC) patient death. MYO10 is upregulated in several tumor types; however, its significance and the underlying mechanism in CRC are not entirely clear. Here, we found that MYO10 was highly expressed in CRC tumor tissues, especially in liver metastasis tissues. MYO10 knockout reduced CRC cell proliferation, invasion, and migration in vitro and CRC metastasis in vivo. We identified RACK1 by LC-MS/MS and demonstrated that MYO10 interacts with and stabilizes RACK1. Mechanistically, MYO10 promotes CRC cell progression and metastasis via ubiquitination-mediated RACK1 degradation and integrin/Src/FAK signaling activation. Therefore, the MYO10/RACK1/integrin/Src/FAK axis may play an important role in CRC progression and metastasis.
Keywords: MYO10; RACK1; colorectal cancer; integrin/Src/FAK signaling; tumorigenesis.
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.