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Published on: April 18, 2025
Lysophosphatidic acid enhances human hepatocellular carcinoma cell migration, invasion and adhesion through P38 MAPK
Bin Zhu1, Song Shi, You-Gang Ma
1The Second Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. zhubindoctor@126.com
Background/Aims:
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.
Methodology:
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.
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