Identification of p130Cas/ErbB2-dependent invasive signatures in transformed mammary epithelial cells

Alessandra Pincini, Giusy Tornillo, Francesca Orso, Marianna Sciortino, Brigitte Bisaro, Maria Del Pilar Camacho Leal, Antonio Lembo, Maria Felice Brizzi, Emilia Turco, Cristiano De Pittà, Paolo Provero, Enzo Medico, Paola Defilippi, Daniela Taverna, Sara Cabodi

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in 3-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY 1) are upregulated, while genes involved in inflammatory response (SAA 1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model.

Original languageEnglish
Pages (from-to)2409-2422
Number of pages14
JournalCell Cycle
Volume12
Issue number15
DOIs
Publication statusPublished - Aug 1 2013

Keywords

  • Breast cancer
  • ErbB2
  • Gene expression
  • Invasion
  • MiRNA
  • P130Cas

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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