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Supervillin (SVIL) is a membrane\u2010associated and actin\u2010binding protein, which is actively involved in the proliferation, spread, and migration of cancer cells. This work investigated CRH's influence on bladder cancer cells'\u00a0migration and relevant mechanisms. By using human bladder cancer cells T24 and RT4 in wound healing experiments and transwell assay, we found that the migration ability of the T24 cells was significantly increased after CRH treatment. In vivo experiments showed that CRH significantly promoted the metastases of T24 cells in cell line\u2010derived xenograft (CDX) mouse model. Interestingly, downregulation of SVIL by SVIL\u2010specifc small hairpin RNAs significantly reduced the promoting effect of CRH on bladder cancer cell migration. Furthermore, CRH significantly increased SVIL\u00a0messenger RNA and protein expression in T24 cells, accompanied with AKT and\u00a0ERK phosphorylation in T24 cells. Pretreatment with AKT inhibitor (MK2206) blocked the CRH\u2010induced SVIL expression and ERK phosphorylation. Also, inhibition of ERK signaling pathway by U0126 significantly reduced the CRH\u2010induced SVIL expression and AKT phosphorylation. It suggested that cross\u2010talking between AKT and ERK pathways was involved in the effect of CRH on SVIL. Taken together, we demonstrated that CRH induced migration of bladder cancer cells, in which AKT and\u00a0ERK pathways \u2010SVIL played a key role.<\/jats:p>","DOI":"10.1002\/cbin.12227","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T04:19:55Z","timestamp":1722572395000},"page":"1743-1754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CRH upregulates supervillin through ERK and AKT pathways to promote bladder cancer cell migration"],"prefix":"10.1002","volume":"48","author":[{"given":"Rongchen","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Basic Medical Sciences Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feier","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Basic Medical Sciences Nanjing Medical University Nanjing 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