RAD23B Promotes Colorectal Cancer Metastasis via the Talin1/Integrin/PI3K/AKT/MMP9 Axis.

BACKGROUND: Radiation sensitive 23 homolog B (RAD23B), a DNA repair-related protein, plays a contributory role in the development of multiple malignancies. This study aimed to explore the role of RAD23B in promoting colorectal cancer (CRC) metastasis and to elucidate the underlying molecular mechanisms. METHODS: RAD23B was overexpressed in CRC cell lines SW480 and HCT-8, with empty vectors serving as controls. Invasion, cell proliferation, and migration were assessed using CCK-8 and Transwell assays. A xenograft mouse model was used to evaluate metastatic potential in vivo. Immunoprecipitation-mass spectrometry (IP-MS) and transcriptomic analysis by RNA sequencing (RNA-seq) were performed to identify signaling pathways regulated by RAD23B. Western blotting was used to analyze the expression of RAD23B, Talin1, Integrins αv/β1, PI3K, p-PI3K, AKT, p-AKT, and MMP9. Immunohistochemistry was conducted to examine RAD23B and Integrin β1 expression in CRC tissues. RESULTS: RAD23B overexpression notably enhanced CRC migration, cell proliferation, and invasion both in vitro and in vivo. IP-MS, RNA-seq, and protein analysis revealed that RAD23B upregulated Talin1 and Integrins αv/β1, resulting in an activation of the PI3K/AKT signaling pathway. Moreover, RAD23B promoted MMP9 expression, contributing to enhanced invasive potential. CONCLUSION: RAD23B facilitates CRC metastasis through activation of the Talin1/Integrin αv/β1/PI3K/AKT/MMP9 signaling axis. These results provide novel insights into the role of RAD23B in CRC progression and identify it as a potential therapeutic target.