Open AccessIdentification of the SUMO E3 ligase PIAS1 as a potential survival biomarker in breast cancer
Author(s) -
Ayan Chanda,
Angela Chan,
Lili Deng,
Elizabeth Kornaga,
Emeka K. Enwere,
Donald G. Morris,
Shirin Bonni
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0177639
Subject(s) - breast cancer , cancer research , metastasis , ubiquitin ligase , cancer , tissue microarray , biomarker , biology , metastatic breast cancer , sumo protein , epithelial–mesenchymal transition , oncology , medicine , ubiquitin , genetics , gene
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.