Involvement of LPA receptor-5 in the enhancement of cell motile activity by phorbol ester and anticancer drug treatments in melanoma A375 cells

Fukushima, Kaori; Takahashi, Kazuhisa; Kurokawa, Aya; Ishimoto, Kaichi; Otagaki, Shiho; Minami, Kanako; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

doi:10.1016/j.bbrc.2018.01.030

Cited by 16 publications

(6 citation statements)

References 19 publications

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“…knockdown reversed the phenomenon [18]. Recent studies on PTC showed that LPAR5 was associated with progression and overall survival in thyroid cancer, which is consistent with our study [19][20][21].…”

Section: Discussionsupporting

confidence: 92%

Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

Fan

Dong

et al. 2020

Preprint

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Abstract Background With the increasing incidence, papillary thyroid cancer (PTC) is receiving more and more attention, but the pathogenesis of which is still not completely elucidated. The purpose of this study was to explore key biomarkers and new therapeutic targets in PTC. Methods GEO2R and Venn online software were used for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software and immunohistochemistry. Results We screened 334 consistently differentially expressed genes (DEGs), composed of 136 upregulated genes and 198 downregulated genes. Gene ontology enrichment analysis suggested that DEGs mainly enriched in the cancer-related pathways and functions. PPI network visualization was performed to select 17 upregulated and 13 downregulated DEGs. Finally, the expression verification and overall survival analysis conducted in the Gene Expression Profiling Interactive Analysis Tool (GEPIA) and UALCAN showed that LPAR5, TFPI and ENTPD1 were related to the development of PTC and the prognosis of PTC patients, and the expression of LPAR5 was verified by tissue chip. Conclusions In summary, the hub genes and pathways identified in the present study not only provided new biomarkers for PTC, but also will be useful for elucidating the pathogenesis of PTC.

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Section: Discussionsupporting

confidence: 92%

Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

Fan

Dong

et al. 2020

Preprint

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“…LPAR5 also participated in anticancer drug treatments in melanoma A375 cells. [30] In human platelet activation, LPAR5 plays a special role by its unique ligand selectivity [31], but few studies have assessed its role in PTC.…”

Section: Discussionmentioning

confidence: 99%

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

Zheng

Xia

et al. 2020

Med Sci Monit

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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/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.

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“…Several groups have reported data concerning LPARs and their roles in melanoma. B16F10 cells predominantly express LPAR2, LPAR5, and LPAR6 [105]. The chemorepellent effect of LPA on B16 melanoma cells was investigated, along with its pro-invasive role [106].…”

Section: Melanomamentioning

confidence: 99%

Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?

Balijepalli

Sitton

Meier

2021

Cells

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Lysophosphatidic acid (LPA) refers to a family of simple phospholipids that act as ligands for G protein-coupled receptors. While LPA exerts effects throughout the body in normal physiological circumstances, its pathological role in cancer is of great interest from a therapeutic viewpoint. The numerous LPA receptors (LPARs) are coupled to a variety of G proteins, and more than one LPAR is typically expressed on any given cell. While the individual receptors signal through conventional GPCR pathways, LPA is particularly efficacious in stimulating cancer cell proliferation and migration. This review addresses the mechanistic aspects underlying these pro-tumorigenic effects. We provide examples of LPA signaling responses in various types of cancers, with an emphasis on those where roles have been identified for specific LPARs. While providing an overview of LPAR signaling, these examples also reveal gaps in our knowledge regarding the mechanisms of LPA action at the receptor level. The current understanding of the LPAR structure and the roles of LPAR interactions with other receptors are discussed. Overall, LPARs provide insight into the potential molecular mechanisms that underlie the ability of individual GPCRs (or combinations of GPCRs) to elicit a unique spectrum of responses from their agonist ligands. Further knowledge of these mechanisms will inform drug discovery, since GPCRs are promising therapeutic targets for cancer.

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Involvement of LPA receptor-5 in the enhancement of cell motile activity by phorbol ester and anticancer drug treatments in melanoma A375 cells

Cited by 16 publications

References 19 publications

Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

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

Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?

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Involvement of LPA receptor-5 in the enhancement of cell motile activity by phorbol ester and anticancer drug treatments in melanoma A375 cells

Cited by 16 publications

References 19 publications

Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

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

Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?

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Involvement of LPA receptor-5 in the enhancement of cell motile activity by phorbol ester and anticancer drug treatments in melanoma A375 cells