학술논문
Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion.
Document Type
Academic Journal
Author
Sciortino M; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Camacho-Leal MDP; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Orso F; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Grassi E; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Costamagna A; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Provero P; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Tam W; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Turco E; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Defilippi P; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Taverna D; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy.; Cabodi S; Department of Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126, Turin, Italy. sara.cabodi@unito.it.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Subject
Language
English
Abstract
ErbB2 overexpression is detected in approximately 20% of breast cancers and is correlated with poor survival. It was previously shown that the adaptor protein p130Cas/BCAR1 is a crucial mediator of ErbB2 transformation and that its overexpression confers invasive properties to ErbB2-positive human mammary epithelial cells. We herein prove, for the first time, that the transcriptional repressor Blimp1 is a novel mediator of p130Cas/ErbB2-mediated invasiveness. Indeed, high Blimp1 expression levels are detected in invasive p130Cas/ErbB2 cells and correlate with metastatic status in human breast cancer patients. The present study, by using 2D and 3D breast cancer models, shows that the increased Blimp1 expression depends on both MAPK activation and miR-23b downmodulation. Moreover, we demonstrate that Blimp1 triggers cell invasion and metastasis formation via its effects on focal adhesion and survival signaling. These findings unravel the previously unidentified role that transcriptional repressor Blimp1 plays in the control of breast cancer invasiveness.