Cellular and Molecular Life Sciences

, Volume 71, Issue 24, pp 4881–4894 | Cite as

Cyclin A2, a novel regulator of EMT

  • Nawal Bendris
  • Caroline T. Cheung
  • Hon Sing Leong
  • John D. Lewis
  • Ann F. Chambers
  • Jean Marie Blanchard
  • Bénédicte Lemmers
Research Article

Abstract

Our previous work showed that Cyclin A2 deficiency promotes cell invasion in fibroblasts. Given that the majority of cancers emerge from epithelia, we explored novel functions for Cyclin A2 by depleting it in normal mammary epithelial cells. This caused an epithelial to mesenchymal transition (EMT) associated with loss of cell-to-cell contacts, decreased E-Cadherin expression and increased invasive properties characterized by a reciprocal regulation of RhoA and RhoC activities, where RhoA-decreased activity drove cell invasiveness and E-Cadherin delocalization, and RhoC-increased activity only supported cell motility. Phenotypes induced by Cyclin A2 deficiency were exacerbated upon oncogenic activated-Ras expression, which led to an increased expression of EMT-related transcriptional factors. Moreover, Cyclin A2-depleted cells exhibited stem cell-like properties and increased invasion in an in vivo avian embryo model. Our work supports a model where Cyclin A2 downregulation facilitates cancer cell EMT and metastatic dissemination.

Keywords

Aggressiveness Cyclin A Invasiveness Stemness 

Abbreviations

CycA2

Cyclin A2

EMT

Epithelial to mesenchymal transition

NMuMG

Normal murine mammary gland

TGFβ

Transforming growth factor β

Supplementary material

Supplementary material 1 (MPG 114 kb)

Supplementary material 2 (MPG 154 kb)

18_2014_1654_MOESM3_ESM.pdf (6.3 mb)
Supplementary material 3 (PDF 6414 kb)

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Nawal Bendris
    • 1
    • 2
    • 3
    • 4
  • Caroline T. Cheung
    • 1
    • 2
    • 3
  • Hon Sing Leong
    • 5
  • John D. Lewis
    • 5
  • Ann F. Chambers
    • 5
  • Jean Marie Blanchard
    • 1
    • 2
    • 3
  • Bénédicte Lemmers
    • 1
    • 2
    • 3
  1. 1.Institut de Génétique Moléculaire de MontpellierCNRSMontpellierFrance
  2. 2.Université Montpellier 2MontpellierFrance
  3. 3.Université Montpellier 1MontpellierFrance
  4. 4.Department of Cell BiologyUT Southwestern Medical CenterDallasUSA
  5. 5.Translational Prostate Cancer Research GroupLondon Regional Cancer ProgramLondonCanada

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