@Article{or.2023.030190,
AUTHOR = {SAYAKA IMATSUJI, YUKIKO UJIE, HIROYUKI ODAKE, MASAYA IMOTO, SUSUMU ITOH, ETSU TASHIRO},
TITLE = {Cisplatin-induced activation of TGF-β signaling contributes to drug resistance},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {1},
PAGES = {139--150},
URL = {http://www.techscience.com/or/v32n1/54650},
ISSN = {1555-3906},
ABSTRACT = {Growing evidence suggests an association between epithelial-mesenchymal transition (EMT), a hallmark of tumor malignancy, and chemoresistance to a number of anti-cancer drugs. However, the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear. To address this issue, we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts. In these clones, the epithelial marker E-cadherin was downregulated, whereas the mesenchymal marker N-cadherin was upregulated. Moreover, the expression of EMT-related transcription factors, including Slug, was elevated. On the other hand, the upregulation of other mesenchymal marker Vimentin was weak, suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones. These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β (TGF-β) receptor kinase inhibitors, indicating that TGF-β signaling is involved in cisplatin-induced the mesenchymal-like phenotypic changes. Moreover, cisplatin was observed to enhance the secretion of TGF-β into the culture media without influencing TGF-β gene transcription. These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-β secretion, ultimately resulting in drug resistance.},
DOI = {10.32604/or.2023.030190}
}