BRAF V600E mutation promoted the growth and chemoresistance of colorectal cancer

• Published in: American journal of cancer research Vol. 13; no. 4; p. 1486
• Main Authors: Ma, Zenghui, Qi, Zhenguang, Gu, Chaofeng, Yang, Zhou, Ding, Yue, Zhou, Yichan, Wang, Wei, Zou, Qi
• Format: Journal Article
• Language: English
• Published: United States 2023
• Subjects: epithelial mesenchymal-transition; chemoresistance; colorectal cancer; invasion; BRAF mutation
• ISSN: 2156-6976; 2156-6976

BRAF mutation occurs frequently in colorectal cancer (CRC), which is associated with poor prognosis. Numerous clinical studies have indicated the undesirable effect of BRAF mutation in CRC patients; however, in vitro studies on the role and functional mechanism of BRAF mutation in CRC are limited. Here, we analyzed the association between BRAF mutation and the clinical features of CRC by using data deposited in the TCGA database. We found that BRAF mutation was closely related to the age and the pathological stage of CRC patients. Additionally, BRAF mutation also indicated poor overall survival in stage II CRC patients. Furthermore, we experimentally explored the function of BRAF mutation by generating a series of HCT116 stable cell lines expressing mutant BRAF , wildtype BRAF , and vector control (NC). We found that BRAF mutation promoted not only the invasion of HCT116 cells through inducing epithelial-mesenchymal transition (EMT), but also cell proliferation as well as the chemoresistance to 5-Fluorouracil (5-FU) and oxaliplatin. Moreover, we confirmed our in vitro findings in mouse xenograft model, in which tumors derived from BRAF expressing HCT116 cells showed significantly increased growth compared with that from HCT116-BRAF and HCT116-NC cells. Consistently, HCT116-BRAF tumors also showed significantly increased resistance to 5-FU compared with HCT116-BRAF and HCT116-NC tumors. Taken together, our study revealed that BRAF mutation not only promoted the progression of CRC via enhancing EMT but also enhanced chemoresistance.