Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells.
OBJECTIVE
The level of lysophosphatidic acid (LPA) is elevated in patients with ovarian cancer, and LPA has been reported to have a pivotal role in cancer dissemination. In the current study, the effect of LPA on the motility of ovarian cancer cells was investigated.


METHODS
We analyzed the effects of LPA on the migration activity, the focal adhesion formation, and the tyrosine phosphorylation of focal adhesion proteins in human ovarian cancer cell lines Caov-3 and OVCAR-3. Inhibitors of the small GTPase Rho, one of its downstream effectors (Rho-associated kinase (ROCK)), myosin light chain kinase (MLCK), and myosin light chain (MLC) phosphatase were used to examine the mechanism of LPA-induced cellular effects.


RESULTS
LPA enhanced the migration of ovarian cancer cells and facilitated their invasion. Rho and ROCK played essential roles in the migratory process, as evidenced by the inhibition of migration and focal adhesion formation of cancer cells by Clostridium botulinum C3 exoenzyme (C3), an inhibitor of Rho, or Y-27632, an inhibitor of ROCK. LPA also evoked the formation of focal adhesions and tyrosine phosphorylation of focal adhesion kinase and paxillin, all of which were inhibited by C3 or Y-27632.


CONCLUSIONS
These results suggest that LPA induced the migration of ovarian cancer cells, at least in part, through accelerated formation of focal adhesions mediated by Rho/ROCK-induced actomyosin contractility. This study may provide the basis for new therapies to control the metastasis of ovarian cancer.
Sawada
Kenjiro
K
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
Morishige
Ken ichirou
Ki
Tahara
Masahiro
M
Ikebuchi
Yoshihide
Y
Kawagishi
Rikako
R
Tasaka
Keiichi
K
Murata
Yuji
Y
D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids / Q000494:pharmacology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D051419:Paxillin; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases
D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; D020741:rho GTP-Binding Proteins