The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness
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Amrita Singh Chandhoke1, Ayan Chanda1,*, Kunal Karve1,*, Lili Deng1, Shirin Bonni1
1Department of Biochemistry and Molecular Biology, and The Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, T2N 4N1, Canada
*Equal second authors
Shirin Bonni, email: [email protected]
Keywords: breast cancer, invasion, sumoylation
Received: September 26, 2016 Accepted: February 07, 2017 Published: February 18, 2017
Tumor metastasis profoundly reduces the survival of breast cancer patients, but the mechanisms underlying breast cancer invasiveness and metastasis are incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts in a sumoylation-dependent manner to suppress the invasive behavior of MDA-MB-231 human breast cancer cell-derived organoids. We also find that the SUMO E3 ligase PIAS3 inhibits the invasive growth of breast cancer cell-derived organoids. In mechanistic studies, PIAS3 maintains breast cancer organoids in a non-invasive state via sumoylation of Smurf2. Importantly, the E3 ubiquitin ligase activity is required for sumoylated Smurf2 to suppress the invasive growth of breast cancer-cell derived organoids. Collectively, our findings define a novel role for the PIAS3-Smurf2 sumoylation pathway in the suppression of breast cancer cell invasiveness. These findings lay the foundation for the development of novel biomarkers and targeted therapeutic approaches in breast cancer.
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