Essential role of STAT5a in DCIS formation and invasion following estrogen treatment

Dees, S; Pontiggia, L; Jasmin, J-F; Sotgia, F; Lisanti, MP; Mercier, I

Abstract

Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment of this pre-invasive disease could benefit from better understanding the pathways involved. While a decreased expression of Caveolin-1 (Cav-1) in the tumor microenvironment of patients with DCIS breast cancer was linked to progression to invasive breast cancer (IBC), the downstream effector(s) contributing to this process remain elusive. The current report shows elevated expression of Signal Transducer and Activator of Transcription 5a (STAT5a) within the DCIS-like lesions in Cav-1 KO mice following estrogen treatment and inhibition of STAT5a expression prevented the formation of these mammary lesions. In addition, STAT5a overexpression in a human DCIS cell line (MCF10DCIS.com) promoted their invasion, a process accelerated by estrogen treatment and associated with increased levels of the matrix metalloproteinase-9 (MMP-9) precursor. In sum, our results demonstrate a novel regulatory axis (Cav-1♦STAT5a♦MMP-9) in DCIS that is fully activated by the presence of estrogen. Our studies suggest to further study phosphorylated STAT5a (Y694) as a potential biomarker to guide and predict outcome of DCIS patient population.

Citation

Dees, S., Pontiggia, L., Jasmin, J., Sotgia, F., Lisanti, M., & Mercier, I. (2020). Essential role of STAT5a in DCIS formation and invasion following estrogen treatment. Aging, 12(14), 15104-15120. https://doi.org/10.18632/aging.103586

• Journal Article Type: Article
• Acceptance Date: Jun 10, 2020
• Online Publication Date: Jul 6, 2020
• Publication Date: Jul 6, 2020
• Deposit Date: Jul 21, 2020
• Publicly Available Date: Jul 21, 2020
• Journal: Aging
• Publisher: Impact Journals
• Volume: 12
• Issue: 14
• Pages: 15104-15120
• DOI: https://doi.org/10.18632/aging.103586
• Keywords: Cav-1, DCIS, STAT5a, estrogen, invasion
• Publisher URL: https://doi.org/10.18632/aging.103586
• Related Public URLs: http://www.impactaging.com/
• Additional Information: Additional Information : ** From PubMed via Jisc Publications Router **Journal IDs: eissn 1945-4589 **Article IDs: pubmed: 32633727; pii: 103586 **History: accepted 10-06-2020; submitted 06-11-2019; Funders : Department of Pharmaceutical Sciences at University of the Sciences