[No authors listed]
Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC) especially in BRAF-like PTC by analyzing TCGA database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5 specific antagonist TC LPA5 4 treatment inhibited CGTH-W3, TPC-1, B-CPAP and BHT-101 cells proliferation, CGTH-W3 and TPC-1 cells migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH-W3 xenograft growth in nude mice. We also found that LPAR5 specific antagonists TC LPA5 4, PI3K inhibitor Wortmannin or mTOR inhibitor Rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH-W3 and TPC-1 cells. Stimulating CGTH-W3 cells transfected with pEGFPC1-Grp1-PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)-triphosphate, which indicates that PI3K was activated by LPA directly. The p110β-siRNA instead of p110α-siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110β. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or PI3K/Akt signal may be the novel therapeutic strategy for treating thyroid cancer.
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