Lysophosphatidic acid enhances human hepatocellular carcinoma cell migration, invasion and adhesion through P38 MAPK pathway.
OBJECTIVE
Lysophosphatidic acid (LPA) has diverse biological activities implicated in tumor progression, including increasing cell migration, invasion and metastasis. However, the underlying mechanisms for LPA-induced human hepatocellular carcinoma (HCC) migration and invasion are poorly understood.


METHODS
We sought to determine the promoting effect of LPA on HCC migration, invasion and adhesion by transwell and matrix adhesion assays, respectively. Levels of matrix metalloproteinase, MMP-2 and MMP- 9 from cells were assayed by ELISA and p38 mitogenactivated protein kinase (MAPK) signaling was determined by western blot analysis.


RESULTS
In the present study, LPA was found to increase HCC cell migration, invasion and adhesion. In addition, LPA increased MMP-9 expression level and induced activation of the p38 mitogen- activated protein kinase (MAPK) signaling. Furthermore, pharmacological inhibition of p38 MAPK signal pathway with SB203580 significantly attenuated LPA-induced HCC cell migration, invasion, and adhesion and abrogated LPA-induced MMP-9 expression and p38 MAPK phosphorylation.


CONCLUSIONS
We demonstrated a mechanism that LPA can activate p38 MAPK signaling, which is required for LPA-induced HCC cell migration, invasion, adhesion and MMP-9 expression, providing a novel biomarker and potential therapeutic target for HCC.
The Second Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. zhubindoctor@126.com
Bin
B
Zhu
Song
S
Shi
You-Gang
YG
Ma
Fei
F
Fan
Zhen-Zhen
ZZ
Yao
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D008246:Lysophospholipids; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C032881:lysophosphatidic acid