Dbl oncogene expression in MCF-10 a epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion

Cristina Vanni, Marzia Ognibene, Federica Finetti, Patrizia Mancini, Sara Cabodi, Daniela Segalerba, Maria Rosaria Torrisi, Sandra Donnini, Maria Carla Bosco, Luigi Varesio, Alessandra Eva

Research output: Contribution to journalArticlepeer-review

Abstract

The proteins of the Dbl family are guanine nucleotide exchange factors (GEFs) of Rho GTPases and are known to be involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders, neoplastic transformation, and tumor metastasis. We have previously demonstrated that expression of Dbl oncogene in lens epithelial cells modulates genes encoding proteins involved in epithelialmesenchymal- transition (EMT) and induces angiogenesis in the lens. Our present study was undertaken to investigate the role of Dbl oncogene in epithelial cells transformation, providing new insights into carcinoma progression.To assess how Dbl oncogene can modulate EMT, cell migration, morphogenesis, and expression of pro-apoptotic and angiogenic factors we utilized bi- and 3-dimensional cultures of MCF-10 A cells. We show that upon Dbl expression MCF-10 A cells undergo EMT. In addition, we found that Dbl overexpression sustains Cdc42 and Rac activation inducing morphological alterations, characterized by the presence of lamellipodia and conferring a high migratory capacity to the cells. Moreover, Dbl expressing MCF-10 A cells form altered 3D structures and can induce angiogenesis by producing proangiogenic factors such as CCL2. These results support a role for Dbl oncogene in epithelial cell differentiation and transformation and suggest the relevance of GEF deregulation in tumor onset and progression.

Original languageEnglish
Pages (from-to)1426-1437
Number of pages12
JournalCell Cycle
Volume14
Issue number9
DOIs
Publication statusPublished - Feb 27 2015

Keywords

  • Angiogenesis
  • Ccl2
  • Dbl oncogene
  • EMT
  • MCF-10 a
  • Migration

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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