Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 684592, 10 pages
http://dx.doi.org/10.1155/2012/684592
Research Article

Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

1Department of Biochemical Sciences, Tuscany Tumor Institute, University of Florence, Morgagni Avenue 50, 50134 Florence, Italy
2Center for Research, Transfer and High Education Study at Molecular and Clinical Level of Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development on Novel Therapies, University of Florence, 50134 Florence, Italy
3Department of Medical Biochemistry, Biology and Physics, University of Bari, Policlinico, G. Cesare Square 70124 Bari, Italy
4Institute of Biomembrane and Bioenergetic, CNR, Amendola Street 176, 70126 Bari, Italy

Received 15 July 2011; Accepted 22 September 2011

Academic Editor: Paolo Pinton

Copyright © 2012 Maria Letizia Taddei et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Increased ROS (cellular reactive oxygen species) are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.