MYO10 contributes to the malignant phenotypes of colorectal cancer via RACK1 by activating integrin/Src/FAK signaling

• Published in: Cancer science Vol. 113; no. 11; pp. 3838 - 3851
• Main Authors: Ou, Haibin, Wang, Lili, Xi, Ziyao, Shen, Hui, Jiang, Yaofei, Zhou, Fuxiang, Liu, Yu, Zhou, Yunfeng
• Format: Journal Article
• Language: English
• Published: Tokyo John Wiley & Sons, Inc 01.11.2022; John Wiley and Sons Inc
• Subjects: Antibodies; Cell migration; Cell proliferation; Colorectal cancer; Colorectal carcinoma; CRISPR; Focal adhesion kinase; integrin/Src/FAK signaling; Kinases; Laboratory animals; Liver; Lung cancer; Mass spectrometry; Metastases; Metastasis; MYO10; Original; Phenotypes; Plasmids; Proteins; RACK1; Scientific imaging; Tumorigenesis; Tumors; Ubiquitination
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15519

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. 1. MYO10 knockout reduced CRC cell proliferation, invasion, and migration in vitro, and CRC metastasis in vivo. 2. We identified RACK1 by LC‐MS/MS and demonstrated that MYO10 interacts with and stabilizes RACK1. 3. MYO10 promotes CRC cell progression and metastasis via ubiquitination‐mediated RACK1 degradation and integrin/Src/FAK signaling activation.