LPA receptor1 antagonists as anticancer agents suppress human lung tumours

Zhao, Pengfei; Wu, Shuang; Li, Yan; Bao, Gegentuya; Pei, Jingyuan; Wang, Yuewu; Ma, Qing; Sun, Haiyan; Damirin, Alatangaole

doi:10.1016/j.ejphar.2019.172886

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…Studies show that LPAR1 enhances metastasis and tumor motility [ 18 ]. Aberrant LPAR1 expressions were observed in many cancer cell lines and primary tumors, including ovarian cancer [ 24 ], breast cancer [ 25 ], liver cancer [ 26 ], gastric cancer [ 27 ], pancreatic cancer [ 28 , 29 ], lung cancer [ 30 , 31 ], glioblastoma (GBM) [ 32 , 33 , 34 ], and osteosarcoma [ 35 ]. Ovarian cancer is the most investigated cancer in studying the malignancy of LPA signaling.…”

Section: Lpa Receptor-mediated Signaling In Cancer Biologymentioning

confidence: 99%

“…Similarly, increased cancer cell invasiveness mediated by LPAR1 was found in pancreatic cancer [ 28 , 29 ]. For lung A549 cancer cells, the LPAR1/Gi/MAP kinase/NF-κB pathway is involved in LPA-induced oncogenesis, and using the LPAR1/3 antagonist Ki16425 to block LPAR1-mediated signaling would significantly reduce tumor volume [ 31 ]. In GBM, LPAR1 expression is also significantly higher than other gliomas [ 32 ].…”

Section: Lpa Receptor-mediated Signaling In Cancer Biologymentioning

confidence: 99%

“…Through LPAR2, BrP-LPA may also sensitize vascular endothelial cells in mice GL-261 glioma cells to improve malignant glioma response to radiation therapy [ 113 ]. Furthermore, Ki16425 is one of the most investigated agents targeting both LPAR1 and LPAR3, and its anti-tumor effects were validated in several cancer cells [ 31 , 114 , 115 ]. As discussed above, Ki16425 may benefit the reduction of chemotherapy-induced NP [ 110 ].…”

Section: Application Of Lpar Agonist/antagonist In Cancermentioning

confidence: 99%

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Lysophosphatidic Acid Receptor Antagonists and Cancer: The Current Trends, Clinical Implications, and Trials

Lin

Chen

2021

Cells

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Lysophosphatidic acid (LPA) is a bioactive lipid mediator primarily derived from membrane phospholipids. LPA initiates cellular effects upon binding to a family of G protein-coupled receptors, termed LPA receptors (LPAR1 to LPAR6). LPA signaling drives cell migration and proliferation, cytokine production, thrombosis, fibrosis, angiogenesis, and lymphangiogenesis. Since the expression and function of LPA receptors are critical for cellular effects, selective antagonists may represent a potential treatment for a broad range of illnesses, such as cardiovascular diseases, idiopathic pulmonary fibrosis, voiding dysfunctions, and various types of cancers. More new LPA receptor antagonists have shown their therapeutic potentials, although most are still in the preclinical trial stage. This review provided integrative information and summarized preclinical findings and recent clinical trials of different LPA receptor antagonists in cancer progression and resistance. Targeting LPA receptors can have potential applications in clinical patients with various diseases, including cancer.

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Section: Lpa Receptor-mediated Signaling In Cancer Biologymentioning

confidence: 99%

Section: Lpa Receptor-mediated Signaling In Cancer Biologymentioning

confidence: 99%

Section: Application Of Lpar Agonist/antagonist In Cancermentioning

confidence: 99%

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Lysophosphatidic Acid Receptor Antagonists and Cancer: The Current Trends, Clinical Implications, and Trials

Lin

Chen

2021

Cells

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“…According to the multiple studies reported, it was believed that the role and expression activity of LPA receptor subtypes in different types of tumors shown an obvious tissue speci city. Several research groups including our group reported that LPA1 closely related to lysophosphatidic acid-induced lung cancer, ovarian cancer and pancreatic cancer progression [4][5][6]. LPA2 and LPA3 was involved in the regulation of chemoresistance in cancer cells treated with CDDP [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…LPA2 and LPA3 was involved in the regulation of chemoresistance in cancer cells treated with CDDP [7,8]. LPA was shown to be a biomarker for other gynecological cancers [9], as well as for gastric cancer and lung cancer [5,10,11]. LPARs, as small molecule targets shown to re ect a potential value in the drugs development of cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

LPA3 is a precise therapeutic target and potential biomarker for ovarian cancer

Zhao

Yun

et al. 2022

Med Oncol

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Current studies have demonstrated that signi cant increased LPA levels to be observed in ascites in patients with ovarian cancer. Although several studies have shown that Lysophosphatidic acid (LPA) related to the progression of ovarian cancer, which LPA receptors (LPARs) and G coupled protein subtypes mediated in LPA actions have not been clearly elucidated. This study aimed to clarify the roles of LPA and it's subtype-speci c LPARs mediating mechanisms in ovarian cancer by integrated using bioinformatic analysis and biological experimental approaches. The big data analysis shown that LPA3 was the only differentially expressed LPA receptor among the six LPARs in ovarian cancer and further veri ed in immunohistochemistry of tissue microarrays. Also found that LPA3 was also highly expressed in ovarian cancer tissue and ovarian cancer cells. Importantly, LPA signi cantly promoted the proliferation and migration of LPA3-overexpressing ovarian cancer cells, while the LPA-induced actions blocked by Ki16425, a LPAR1/3 antagonist treated, and LPA3-shRNA transfected. In vivo study indicated that the LPA3-overexpressing cell derived tumors metastasis, tumors volume and tumors mass were apparently increased in xenografted nude mice. In addition, we also observed that LPA3 was differential high-expression in ovarian cancer tissue of the patients. Our studies further con rmed the LPA3/Gi/MAPKs/NF-κB signals were involved in LPA-induced oncogenic actions in ovarian cancer cells. Our ndings indicated that the LPA3 might be a novel precise therapeutic target and potential biomarker for ovarian cancer.

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LPAR2-mediated action promotes human renal cell carcinoma via MAPK/NF-κB signaling to regulate cytokine network

Wang

et al. 2022

J Cancer Res Clin Oncol

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LPA receptor1 antagonists as anticancer agents suppress human lung tumours

Cited by 14 publications

References 29 publications

Lysophosphatidic Acid Receptor Antagonists and Cancer: The Current Trends, Clinical Implications, and Trials

Lysophosphatidic Acid Receptor Antagonists and Cancer: The Current Trends, Clinical Implications, and Trials

LPA3 is a precise therapeutic target and potential biomarker for ovarian cancer

LPAR2-mediated action promotes human renal cell carcinoma via MAPK/NF-κB signaling to regulate cytokine network

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