Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

Ayan Chanda; Angela Chan; Lili Deng; Elizabeth N Kornaga; Emeka K Enwere; Donald G Morris; Shirin Bonni

doi:10.1371/journal.pone.0177639

Identification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer

PLoS One. 2017 May 11;12(5):e0177639. doi: 10.1371/journal.pone.0177639. eCollection 2017.

Authors

Ayan Chanda¹, Angela Chan², Lili Deng¹, Elizabeth N Kornaga², Emeka K Enwere², Donald G Morris^{2

3}, Shirin Bonni¹

Affiliations

¹ Arnie Charbonneau Cancer Institute and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
² Translational Laboratories, Tom Baker Cancer Centre, Alberta Health Services, Calgary, Alberta, Canada.
³ Department of Oncology, Alberta Health Services, Calgary, Alberta, Canada.

Abstract

Metastasis is the ultimate cause of breast cancer related mortality. Epithelial-mesenchymal transition (EMT) is thought to play a crucial role in the metastatic potential of breast cancer. Growing evidence has implicated the SUMO E3 ligase PIAS1 in the regulation of EMT in mammary epithelial cells and breast cancer metastasis. However, the relevance of PIAS1 in human cancer and mechanisms by which PIAS1 might regulate breast cancer metastasis remain to be elucidated. Using tissue-microarray analysis (TMA), we report that the protein abundance and subcellular localization of PIAS1 correlate with disease specific overall survival of a cohort of breast cancer patients. In mechanistic studies, we find that PIAS1 acts via sumoylation of the transcriptional regulator SnoN to suppress invasive growth of MDA-MB-231 human breast cancer cell-derived organoids. Our studies thus identify the SUMO E3 ligase PIAS1 as a prognostic biomarker in breast cancer, and suggest a potential role for the PIAS1-SnoN sumoylation pathway in controlling breast cancer metastasis.

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / metabolism*
Breast Neoplasms / enzymology*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Nucleus / drug effects
Cell Nucleus / metabolism
Cell Proliferation / drug effects
Cohort Studies
Female
HEK293 Cells
Humans
Middle Aged
Neoplasm Invasiveness
Organoids / drug effects
Protein Inhibitors of Activated STAT / metabolism*
Protein Stability / drug effects
Protein Transport / drug effects
Small Ubiquitin-Related Modifier Proteins / metabolism*
Sumoylation / drug effects
Survival Analysis
Tissue Array Analysis
Transforming Growth Factor beta / pharmacology

Substances

Biomarkers, Tumor
PIAS1 protein, human
Protein Inhibitors of Activated STAT
Small Ubiquitin-Related Modifier Proteins
Transforming Growth Factor beta

Grants and funding

This work was supported by the University of Calgary, Achievers in Medical Sciences Recruitment Award and Eyes High Recruitment Award; the Breast Cancer Society of Canada Grant; the Canadian Institutes of Health Research; Alberta Innovates—Health Solutions and the Canadian Breast Cancer Foundation Prairies/NWT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.