S100A6 mediated epithelial-mesenchymal transition affects chemosensitivity of colorectal cancer to oxaliplatin.

Chunying Zhang, Menglu Zeng, Yihan Xu, Bihan Huang, Pengchong Shi, Xianjin Zhu, Yingping Cao

Gene 2024 Jul 01

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To investigate the mechanism by which S100 calcium-binding protein A6 (S100A6) affects colorectal cancer (CRC) cells to oxaliplatin (L-OHP) chemotherapy, and to explore new strategies for CRC treatment. S100A6 expression was assessed in both parental and L-OHP-resistant CRC cells using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA). Lentiviral vectors were utilized to induce the knockdown of S100A6 expression, followed by comprehensive evaluations of cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Additionally, RNA-seq analysis was conducted to identify genes associated with the knockdown of S100A6. Elevated S100A6 expression in CRC tissues correlated with an adverse prognosis in patients with CRC. Higher expression of S100A6 was also observed in L-OHP-resistant CRC cells, which showed enhanced proliferation, migration, invasion, and antiapoptotic capabilities. Notably, the knockdown of S100A6 expression resulted in decreased proliferation, increased apoptosis, and suppression of EMT and tumorigenicity in L-OHP-resistant CRC cells. Transcriptome sequencing reveals a noteworthy association between S100A6 and vimentin expression. Application of the EMT agonist, transforming growth factor β (TGF-β), induces EMT in CRC cells. S100A6 expression positively correlates with TGF-β expression. TGF-β facilitated the expression of EMT-related molecules and reduced the chemosensitivity of L-OHP in S100A6-knockdown cells. In conclusion, the knockdown of S100A6 may overcome the L-OHP resistance of CRC cells by modulating EMT. Copyright © 2024 Elsevier B.V. All rights reserved.

Citation

Chunying Zhang, Menglu Zeng, Yihan Xu, Bihan Huang, Pengchong Shi, Xianjin Zhu, Yingping Cao. S100A6 mediated epithelial-mesenchymal transition affects chemosensitivity of colorectal cancer to oxaliplatin. Gene. 2024 Jul 01;914:148406