The TCF7L2/miR-206/Cofilin1 axis promotes the metastasis of bladder cancer cells by regulating the formation of invadopodiaOA
Bladder cancer(BCa)is one of the most common malignant tumors of the urinary system,but its pathogenesis is still unclear.T1G3 BCa is particularly invasive and relapses readily after treatment,with progression to invasive cancer or distant metastasis.Therefore,identification of the molecular mechanism by which it invades and metastasizes to guide treatment and predict patient prognosis is needed.Cofilin1 plays an important role in regulating gene expression and the invasiveness of tumors.In this study,we show that Cofilin1 is highly expressed in BCa and lymph nodes with metastasis,which is positively related to the grade of BCa,and is significantly related to clinicopathological parameters and cancer-specific survival.Phenotypic analysis reveals that Cofilin1 knockout inhibits the proliferation and migration of BCa cells,whereas Cofilin1 overexpression promotes the opposite phenotype.Cofilin1 binds to cortactin,thereby reducing the expression of F-actin and promoting the formation of invadopodia in BCa cells.Further experiments reveal that TCF7L2 can bind to the promoter of Cofilin1 and transactivate it,promoting a malignant phenotype.TCF7L2 may also reverse the inhibitory effect of miR-206 on the binding of Cofilin1 and cortactin and promote the metastasis of BCa by inhibiting the transcription maturation of miR-206.This study confirms that Cofilin1 is an oncogene in T1G3 BCa,and the TCF7L2/miR-206/Cofilin1 signaling pathway plays an important role in the formation of invadopodia in BCa.
Yuzhen Jie;Yinggui Yang;Chengyan Guo;Qinghui Wu;Zhewen Ou;Weifu Wang;Ning Xu;Wei Peng;Yingguang Wu;Jiangfan Peng;Shengchao Ma;Shufang Zhang;Fei Wang
Department of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,China School of Clinical Medicine,Hainan Medical University,Haikou 571199,ChinaDepartment of Urology,Shenzhen Hospital of Southern Medical University,Shenzhen 518110,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,China School of Clinical Medicine,Hainan Medical University,Haikou 571199,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,China School of Clinical Medicine,Hainan Medical University,Haikou 571199,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,China School of Clinical Medicine,Hainan Medical University,Haikou 571199,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,China School of Clinical Medicine,Hainan Medical University,Haikou 571199,ChinaDepartment of Urology,Shenzhen Hospital of Southern Medical University,Shenzhen 518110,ChinaNHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan 750004,ChinaCentral Laboratory,Haikou Affiliated Hospital of Central South University Xiangya School of Medicine and Haikou City Key Laboratory of Clinical Medicine,Haikou 570203,ChinaDepartment of Urology,Affiliated Hainan Hospital of Hainan Medical University,Hainan General Hospital,Hainan Provincial Clinical Medical Center,Haikou 570311,China School of Clinical Medicine,Hainan Medical University,Haikou 571199,China
医药卫生
bladder cancermetastasisCofilin1invadopodia formation
《Acta Biochimica et Biophysica Sinica》 2026 (3)
P.663-680,18
supported by the grants from the National Natural Science Foundation of China(Nos.81760461,82060461,82460553)the Hainan Provincial Innovative Research Team Project(No.820CXTD447).
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