Cofilin 1 promotes bladder cancer and is regulated by TCF7L2

Abstract

Earlier reports demonstrated that Cofilin expression is increased in bladder cancer samples, though its function remains unknown. Here, we found that Cofilin 1 expression was higher in bladder cancer tissues than in paracancerous tissues. Overexpression of Cofilin 1 promoted, while Cofilin 1 knockdown inhibited, proliferation, migration, and invasion in the T24 and RT4 bladder cancer cell lines. In addition, Cofilin 1 overexpression increased, while Cofilin 1 knockdown decreased, bladder tumor volumes in mouse xenograft experiments. Transcription factor 7-like 2 (TCF7L2) targeted the promoter of the Cofilin 1 gene, and TCF7L2 knockdown or mutations in the Cofilin 1 promoter dramatically decreased Cofilin 1 transcription. TCF7L2 promoted cell proliferation and migration and increased Cofilin 1 protein levels in RT4 and T24 cells. Thus, TCF7L2 contributed to Cofilin 1-induced promotion of bladder cancer development by binding to the Cofilin 1 promoter and increasing its expression.

Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma

“…By CCK8 and clone formation assays, we found that shRNA lentivirus-mediated cofilin-2 silencing inhibited the proliferative activity of CNE-2R cells at different radiation doses. Wang et al showed that downregulation of cofilin 1 could inhibit cell proliferation in the human bladder cancer RT4 cell line [ 39 ], corroborating our findings. Cofilin promotes apoptosis in gastric cancer BGC-823 and SGC-7901 cells via mitochondrial translocation and induces mitochondrial damage and cytochrome c release; therefore, it may be a key target for the treatment of gastric cancer in the future [ 40 , 41 ].…”

“…Cofilin promotes apoptosis in gastric cancer BGC-823 and SGC-7901 cells via mitochondrial translocation and induces mitochondrial damage and cytochrome c release; therefore, it may be a key target for the treatment of gastric cancer in the future [ 40 , 41 ]. In addition, studies have shown that cofilin inhibition or silencing increases cell apoptosis in human bladder cancer RT4 cells and resistant HCC cells [ 39 , 42 ]. ShRNA-mediated knockdown of cofilin-2 enhanced apoptosis in CNE-2R cells, as demonstrated by flow cytometry in this study.…”

Diallyl disulfide induces downregulation and inactivation of cofilin�1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells

“…The present study verified that DADS gradually decreased the mRNA and protein expression, as well as the phosphorylation of cofilin 1 in HL-60 cells in a time-dependent manner. Cofilin-1, an actin depolymerizing factor (ADF)/cofilin superfamily member, has been shown to be highly expressed in a number of cancer types and is associated with proliferation, migration, invasion, differentiation, metastasis and poor prognosis (16,21). The expression level of cofilin and its subcellular distribution play important roles in the high migratory ability of tumor cells (22).…”

Circulating Actin-Binding Proteins in Progression of Laryngeal and Hypoharyngeal Cancers

“…Актин-связывающие белки, кроме обеспечения локомоции, ассоциированы с другими клеточными процессами: пролиферацией, апоптозом, эндо-и экзоцитозом. Важное значение в развитии злокачественных опухолей принадлежит актинсвязывающим белкам: кофилину, профилину, эзрину, фасцину и аденилил-циклаза ассоциированному протеину 1 (САР1) [3][4][5][6][7][8][9]. Основная функция САР1 у эукариот -регуляция реконструкции актина в ответ на клеточные сигналы.…”