Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion

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-positiv...

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Autores principales:	Marianna Sciortino, Maria del Pilar Camacho-Leal, Francesca Orso, Elena Grassi, Andrea Costamagna, Paolo Provero, Wayne Tam, Emilia Turco, Paola Defilippi, Daniela Taverna, Sara Cabodi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c219a533573a4869ae802e7d793d8eef
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spelling	oai:doaj.org-article:c219a533573a4869ae802e7d793d8eef2021-12-02T11:52:20ZDysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion10.1038/s41598-017-01332-z2045-2322https://doaj.org/article/c219a533573a4869ae802e7d793d8eef2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01332-zhttps://doaj.org/toc/2045-2322Abstract 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.Marianna SciortinoMaria del Pilar Camacho-LealFrancesca OrsoElena GrassiAndrea CostamagnaPaolo ProveroWayne TamEmilia TurcoPaola DefilippiDaniela TavernaSara CabodiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marianna Sciortino Maria del Pilar Camacho-Leal Francesca Orso Elena Grassi Andrea Costamagna Paolo Provero Wayne Tam Emilia Turco Paola Defilippi Daniela Taverna Sara Cabodi Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion
description	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.
format	article
author	Marianna Sciortino Maria del Pilar Camacho-Leal Francesca Orso Elena Grassi Andrea Costamagna Paolo Provero Wayne Tam Emilia Turco Paola Defilippi Daniela Taverna Sara Cabodi
author_facet	Marianna Sciortino Maria del Pilar Camacho-Leal Francesca Orso Elena Grassi Andrea Costamagna Paolo Provero Wayne Tam Emilia Turco Paola Defilippi Daniela Taverna Sara Cabodi
author_sort	Marianna Sciortino
title	Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion
title_short	Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion
title_full	Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion
title_fullStr	Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion
title_full_unstemmed	Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion
title_sort	dysregulation of blimp1 transcriptional repressor unleashes p130cas/erbb2 breast cancer invasion
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c219a533573a4869ae802e7d793d8eef
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Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion

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