Deletion of SMURF 1 represses ovarian cancer invasion and EMT by modulating the DAB2IP/AKT/Skp2 feedback loop. Issue 6 (22nd January 2019)

• Record Type: Journal Article
• Authors: Fan, Xiuhua; Wang, Yan; Fan, Jiajia; Chen, Rui
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 6(2019)
• Page Start: 10643
• Page End: 10651
• Publication Date: 2019-01-22
• Subjects: DAB2IP/AKT/Skp2 signaling -- epithelial‐to‐mesenchymal transition -- invasion -- ovarian cancer -- SMAD ubiquitination regulatory factor 1; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28354
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: SMAD ubiquitination regulatory factor 1 (SMURF1) has been described as a tumor suppressor in multiple aggressive cancers. Nevertheless, the potential role of SMURF1 in ovarian cancer invasion and epithelial‐to‐mesenchymal transition (EMT) remains unclear. The aim of this study was to evaluate the efficacy of SMURF1 on tumor migration and EMT and elucidate the underlying molecular mechanism in ovarian carcinoma. We found elevated SMURF1 in several ovarian cancer cells in both messenger RNA and protein. Additionally, silencing SMURF1 apparently repressed cell proliferation and invasion capacity of SKOV3 and A2780 cells and markedly attenuated expression of linked proteins such as proliferating cellnuclear antigen, matrix metalloproteinase (MMP)‐2, and MMP‐9. Furthermore, depletion of SMURF1 dramatically impeded EMT progress by modulating EMT biomarkers, with a notable increase in E‐cadherin expression accompanied by the decrease in N‐cadherin and vimentin in both SKOV3 and A2780 cells. Interestingly, elimination of SMURF1 led to disabled homolog 2 DOC‐2/DAB2 interacting protein (DAB2IP) activation and dampened AKT/Skp2 signaling. Most important, depleted of DAB2IP or treatment with the AKT agonist 740Y‐P effectively abolished the suppressive effects of SMURF1 knockout on cell invasiveness and EMT process. Taken all data together, these findings demonstrated that the absence of SMURF1 repressed cell proliferation, invasive capability, and EMT process in ovarian cancer through DAB2IP/AKT/Skp2 signaling loops, suggesting that SMURF1 may serve as a new potential therapeutic agent for ovarian cancer. Abstract : These findings demonstrated that the absence of SMAD ubiquitination regulatory factor 1 (SMURF1) repressed cell proliferation, invasive capability, and epithelial‐to‐mesenchymal transition process in ovarian cancer through DAB2IP/AKT/Skp2 signaling loops, suggesting that SMURF1 may serve as a new potential therapeutic agent for ovarian cancer.