YAP mediates apoptosis through failed integrin adhesion reinforcement

Lidan Shi, Elisabeth Nadjar-Boger, Hamidreza Jafarinia, Aurélie Carlier, Haguy Wolfenson*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Extracellular matrix (ECM) rigidity is a major effector of cell fate decisions. Whereas cell proliferation on stiff matrices, wherein Yes-associated protein (YAP) plays a pivotal role, is well documented, activation of apoptosis in response to soft matrices is poorly understood. Here, we show that YAP drives the apoptotic decision as well. We find that in cells on soft matrices, YAP is recruited to small adhesions, phosphorylated at the Y357 residue, and translocated into the nucleus, ultimately leading to apoptosis. In contrast, Y357 phosphorylation levels are dramatically low in large adhesions on stiff matrices. Furthermore, mild attenuation of actomyosin contractility allows adhesion growth on soft matrices, leading to reduced Y357 phosphorylation levels and resulting in cell growth. These findings indicate that failed adhesion reinforcement drives rigidity-dependent apoptosis through YAP and that this decision is not determined solely by ECM rigidity but rather by the balance between cellular forces and ECM rigidity.
Original languageEnglish
Article number113811
JournalCell Reports
Volume43
Issue number3
DOIs
Publication statusPublished - 21 Feb 2024

Keywords

  • CP: Cell biology
  • Src
  • YAP
  • actomyosin
  • anchorage-independence
  • apoptosis
  • c-Abl
  • mechanosensing
  • pYAP-Y357
  • rigidity sensing

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