@Article{or.2025.067535,
AUTHOR = {Jun Li, Yang Chen, Zhijiao Hao, Zhiyong Zhang, Jingyi Fan, Xiao Liu, Xueli Zhao, Hongyan Zhang, Chenpeng Wu},
TITLE = {RAD23B Promotes Colorectal Cancer Metastasis via the Talin1/Integrin/PI3K/AKT/MMP9 Axis},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {11},
PAGES = {3523--3541},
URL = {http://www.techscience.com/or/v33n11/64072},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> 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. <b>Methods:</b> 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 <i>in vivo</i>. 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. <b>Results:</b> RAD23B overexpression notably enhanced CRC migration, cell proliferation, and invasion both <i>in vitro</i> and <i>in vivo</i>. 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. <b>Conclusion:</b> 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.},
DOI = {10.32604/or.2025.067535}
}