biostudies-literatureIyengar PVDutch Research Council (NWO)Cancer Genomics CentreH2020 Marie Skłodowska-Curie ActionsLeids Universitair Medisch CentrumKWF Kankerbestrijding1516-1531https://www.ebi.ac.uk/biostudies/studies/S-EPMC9530648biostudies-literatureUnknown20(10)Patients with bladder cancer often have a poor prognosis due to the highly invasive and metastatic characteristics of bladder cancer cells. Epithelial-to-mesenchymal transition (EMT) has been causally linked to bladder cancer invasion. The E3 ubiquitin ligase, tumor necrosis factor receptor-associated factor 4 (TRAF4) has been implicated as a tumor promoter in a wide range of cancers. In contrast, here we show that low TRAF4 expression is associated with poor overall survival in patients with bladder cancer. We show that the TRAF4 gene is epigenetically silenced and that ERK mediates TRAF4 phosphorylation, resulting in lower TRAF4 protein levels in bladder cancer cells. In addition, we demonstrate that TRAF4 is inversely correlated with an EMT gene signature/protein marker expression. FuncMolecular cancer research : MCRTRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.PMC9530648016.176.081BUIT 2015-7526Veni- 016.176.081Gisela ThierSuriyamurthy STen Dijke PXie Fvan Dinther MTan TZMei HVerma CSLama DMarvin DLIyengar PVZhang LRitsma LfalseTRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.Patients with bladder cancer often have a poor prognosis due to the highly invasive and metastatic characteristics of bladder cancer cells. Epithelial-to-mesenchymal transition (EMT) has been causally linked to bladder cancer invasion. The E3 ubiquitin ligase, tumor necrosis factor receptor-associated factor 4 (TRAF4) has been implicated as a tumor promoter in a wide range of cancers. In contrast, here we show that low TRAF4 expression is associated with poor overall survival in patients with bladder cancer. We show that the TRAF4 gene is epigenetically silenced and that ERK mediates TRAF4 phosphorylation, resulting in lower TRAF4 protein levels in bladder cancer cells. In addition, we demonstrate that TRAF4 is inversely correlated with an EMT gene signature/protein marker expression. Func2022-01-01T00:00:00Z2022 Oct2026-05-27T22:31:09.633Z2025-02-19T02:37:59.191ZS-EPMC95306483573121210.1158/1541-7786.MCR-20-1029