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06 January 2020 : Laboratory Research  

Lysophosphatidic Acid Receptor 5 (LPAR5) Plays a Significance Role in Papillary Thyroid Cancer via Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (mTOR) Pathway

Cheng-Yong Wu1ABC, Chen Zheng1C, Er-Jie Xia1D, Rui-Da Quan1C, Jing Hu1D, Xiao-Hua Zhang1EFG, Ru-Tian Hao1AD*

DOI: 10.12659/MSM.919820

Med Sci Monit 2020; 26:e919820


BACKGROUND: Thyroid cancer is the most common endocrine system malignancy. Scientists have done considerable research into the molecular mechanisms involved, but many mechanisms remain undiscovered.

MATERIAL AND METHODS: We performed a comprehensive analysis of the whole-transcriptome resequencing derived from thyroid tissues and paired papillary thyroid cancer (PTC) and showed that lysophosphatidic acid receptor 5 (LPAR5) is strongly overexpressed in thyroid carcinoma. Then, we used TPC-1 and KTC-1 to explore the effect of LPAR5 knockdown on colony formation, migration, proliferation, invasion, and apoptosis of PTC cell line cells. AKT activator was used for the recovery test. Finally, we designed proteomic experiments to explore the role of LPAR5 in the AKT pathway and the EMT process.

RESULTS: Cell function experiments showed that LPAR5 knockdown can significantly induce apoptosis of KTC-1 and TPC-1 cells. Furthermore, LPAR5 can promote PTC metastasis and tumorigenesis by activating the PI3K/AKT pathway and decreasing its cancer-promoting effect when using AKT agonist. We also found that LPAR5 can regulate the expression of EMT-related proteins, which affect invasion and migration.

CONCLUSIONS: In summary, downregulation of LPAR5 expression can inhibit the physiological process of PTC, and this phenomenon is related to the PI3K/AKT pathway and EMT.

Keywords: Oncogene Protein v-akt, Receptors, Lysophosphatidic Acid, phosphatidylinositol 3-kinase, Proteomics, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Thyroid Cancer, Papillary, Thyroid Gland

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750