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.
Highlights
Metastasis is the major cause of cancer related mortality [1]
The small ubiquitin like modifier (SUMO) E3 ligase PIAS1 inhibits the invasive behaviour of breast cancer cells grown in a three-dimensional model system, and deregulation of PIAS1 activity promotes the growth of breast cancer cell-derived metastases in a xenograft mouse model [11]
We have identified the SUMO E3 ligase PIAS1 as a biologically relevant biomarker in breast cancer that predicts patient survival
Summary
Metastasis is the major cause of cancer related mortality [1]. The mechanisms that control the invasive growth and metastatic potential of breast cancer remain incompletely understood [2]. Epithelial-mesenchymal transition (EMT) is thought to play a key role in tumor metastasis [3,4,5]. EMT promotes the transdifferentiation of epithelial cells into migratory, invasive, and mesenchymal-like cells [3]. Carcinoma cells undergoing EMT can escape from primary tumor sites, enter the circulation, and move out to invade distant sites where secondary tumors or metastases form [6,7]. Identifying regulators of EMT should provide insights into the mechanisms that control tumor metastasis and patient survival
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
