ATX/LPA axis regulates FAK activation, cell proliferation, apoptosis, and motility in human pancreatic cancer cells.

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Date: Apr. 2022
Publisher: Springer
Document Type: Report; Brief article
Length: 312 words

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Keywords: Lysophosphatidic acid; Proliferation; Apoptosis; Cell motility; Pancreatic cancer Abstract Previous studies implicated ATX/LPA axis as a potential driver of tumorigenesis and progression in pancreatic cancer. This study aimed to determine the existence of the autocrine pathway of ATX/LPA action in pancreatic cancer cells, and to elucidate its influence on focal adhesion kinase (FAK) activation, cellular proliferation, apoptosis, and migration. Firstly, we identified the lysophosphatidic acid (LPA) concentrations in cultured cell supernatant by ELISA and observed the effect of the autotaxin (ATX)-specific inhibitor S32826 on LPA concentrations. We found the existence of a certain concentration of LPA in cellular supernatant, which was significantly decreased by S32826 in a dose- and time-dependent manner. A maximum response was observed at 50 µM for 72 h. Secondly, the effect of S32826 on the protein expression and intracellular sublocalization of total FAK and phosphorylated FAK (pY397 FAK) was determined by Western blot and immunofluorescence staining. It was found that the expression of total FAK and pY397 FAK and their distribution along the cell membrane where adhesion structures are located were significantly decreased by S32826. Finally, we observed the influence of S32826 on cell proliferation, apoptosis, and migration by CCK-8 assay, flow cytometric analysis, and transwell migration assay. Results showed that cell viability and migration were significantly declined, and the proportions of apoptotic cells were significantly increased by S32826. This study verified the existence of autocrine regulation of LPA secretion via producing ATX by pancreatic cancer cells in vitro and the important role of LPA/ATX axis on FAK activation, cell proliferation, apoptosis, and motility. Author Affiliation: (1) Department of Gastroenterology, Wuhan No.1 Hospital (Wuhan Integrated TCM and Western Medicine Hospital), No. 215, Zhongshan Road, 430022, Wuhan, Hubei, China (2) Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China (d) Article History: Registration Date: 02/14/2022 Received Date: 12/04/2021 Accepted Date: 02/14/2022 Online Date: 04/14/2022 Byline:

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Gale Document Number: GALE|A702795690