Oncotarget

Research Papers:

The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness

Amrita Singh Chandhoke, Ayan Chanda, Kunal Karve, Lili Deng and Shirin Bonni _

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Oncotarget. 2017; 8:21001-21014. https://doi.org/10.18632/oncotarget.15471

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Abstract

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

Correspondence to:

Shirin Bonni, email: [email protected]

Keywords: breast cancer, invasion, sumoylation

Received: September 26, 2016     Accepted: February 07, 2017     Published: February 18, 2017

ABSTRACT

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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