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

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

Author information

1
Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
2
Cancer Biology Graduate Program, Emory University, Atlanta, GA 30322, USA.
3
Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
4
Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
5
Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA lboise@emory.edu.

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

PMID:
24610949
PMCID:
PMC4021471
DOI:
10.1242/jcs.135137
[Indexed for MEDLINE]
Free PMC Article

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