Mitochondrial Dysfunction and Reactive Oxygen Species Imbalance Promote Breast Cancer Cell Motility through a CXCL14-Mediated Mechanism

Although mitochondrial dysfunction and reactive oxygen species (ROS) stress have long been observed in cancer cells, their role in promoting malignant cell behavior remains unclear. Here, we show that perturbation of the mitochondrial respiratory chain in breast cancer cells leads to a generation of...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2009-03, Vol.69 (6), p.2375-2383
Main Authors: PELICANO, Helene, WEIQIN LU, YAN ZHOU, WAN ZHANG, ZHAO CHEN, YUMIN HU, PENG HUANG
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Calcium - metabolism
Cell Line, Tumor
Cell Movement - physiology
Chemokines, CXC - metabolism
Cytosol - metabolism
Female
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Mice
Mice, Inbred BALB C
Mitochondria - metabolism
Neoplasm Invasiveness
Oxygen Consumption
Pharmacology. Drug treatments
Reactive Oxygen Species - metabolism
Signal Transduction
Transcription Factor AP-1 - metabolism
Tumors
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Summary:Although mitochondrial dysfunction and reactive oxygen species (ROS) stress have long been observed in cancer cells, their role in promoting malignant cell behavior remains unclear. Here, we show that perturbation of the mitochondrial respiratory chain in breast cancer cells leads to a generation of subclones of cells with increased ROS, active proliferation, high cellular motility, and invasive behaviors in vitro and in vivo. Gene expression analysis using microarrays revealed that all subclones overexpressed CXCL14, a novel chemokine with undefined function. We further show that CXCL14 expression is up-regulated by ROS through the activator protein-1 signaling pathway and promotes cell motility through elevation of cytosolic Ca(2+) by binding to the inositol 1,4,5-trisphosphate receptor on the endoplasmic reticulum. Abrogation of CXCL14 expression using a decoy approach suppressed cell motility and invasion. Our data suggest that mitochondrial dysfunction and ROS stress promote cancer cell motility through a novel pathway mediated by CXCL14.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-3359