title: Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independently of catalytic function.
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.
authors.affiliation: 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.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brentnall
authors.affiliation: Cancer Biology Graduate Program, Emory University, Atlanta, GA 30322, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Weir
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rongvaux
authors.affiliation: Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Marcus
authors.affiliation: Departments of Hematology and Medical Oncology and Cell Biology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA lboise@emory.edu.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Boise
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D002384:Catalysis; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D051379:Mice
chemical_list: D005353:Fibronectins; D053148:Caspase 3
keywords: Adhesion; Caspase; Migration