Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independently of catalytic function

J Cell Sci. 2014 May 15;127(Pt 10):2217-26. doi: 10.1242/jcs.135137. Epub 2014 Mar 7.

Abstract

Caspase-3 is an effector caspase that is activated downstream of mitochondrial outer-membrane permeabilization (MOMP) during apoptosis. However, previous work has demonstrated that caspase-3-deficient mouse embryonic fibroblasts (MEFs) are resistant to mitochondrially mediated cell death and display a delay in the mitochondrial events of apoptosis, including Bax activation, MOMP and release of cytochrome c. Here, we show that caspase-3 regulates fibronectin secretion and impacts on cell morphology, adhesion and migration. Surprisingly, the catalytic activity of caspase-3 is not required for these non-apoptotic functions. Moreover, we found that caspase-3-deficient MEFs are not resistant to death by anoikis and that exogenous fibronectin protects wild-type MEFs from cell death induced by serum withdrawal. Taken together, our data indicate that procaspase-3 has a non-apoptotic function; it regulates the secretion of fibronectin and influences morphology, adhesion and migration. Furthermore, this novel procaspase-3 function might alter the apoptotic threshold of the cell.

Keywords: Adhesion; Caspase; Migration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Caspase 3 / metabolism*
  • Catalysis
  • Cell Adhesion / physiology*
  • Cell Movement / physiology*
  • Cell Survival / physiology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibronectins / metabolism*
  • Mice

Substances

  • Fibronectins
  • Caspase 3