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Pré-Publication, Document De Travail Année : 2020

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Diala Kantar
  • Fonction : Auteur
Emilie Bousquet Mur
  • Fonction : Auteur
Vera Slaninova
Yezza Ben Salah
  • Fonction : Auteur
Luca Costa
Elodie Forest
  • Fonction : Auteur
Charles Géminard
  • Fonction : Auteur
Marion Larroque
  • Fonction : Auteur
Florence Boissière-Michot
Béatrice Orsetti
  • Fonction : Auteur
Charles Theillet
  • Fonction : Auteur
Jacques Colinge
Christine Benistant
  • Fonction : Auteur
Antonio Maraver
  • Fonction : Auteur
Lisa Heron-Milhavet
Alexandre Djiane

Résumé

Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.

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Diala Kantar, Emilie Bousquet Mur, Vera Slaninova, Yezza Ben Salah, Luca Costa, et al.. MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis. 2020. ⟨hal-03066045⟩
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