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USP4 promotes the proliferation and glucose metabolism of gastric cancer cells by upregulating PKM2

Background The pyruvate kinase enzyme PKM2 catalyzes the final step in glycolysis and converts phosphoenolpyruvate (PEP) to pyruvate. PKM2 is often overexpressed in cancer and plays a role in the Warburg effect. The expression of PKM2 can be regulated at different levels. While it has been proven th...

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Bibliographic Details
Published in:PloS one 2023-08, Vol.18 (8), p.e0290688-e0290688
Main Authors: Chen, Yuanyuan, Guo, Yunfei, Yuan, Mei, Guo, Song, Cui, Shuaishuai, Chen, Dahu
Format: Article
Language:English
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Summary:Background The pyruvate kinase enzyme PKM2 catalyzes the final step in glycolysis and converts phosphoenolpyruvate (PEP) to pyruvate. PKM2 is often overexpressed in cancer and plays a role in the Warburg effect. The expression of PKM2 can be regulated at different levels. While it has been proven that PKM2 can be regulated by ubiquitination, little is known about its de-ubiquitination regulation. Methods Immunoprecipitation was applied to identify the PKM2 interaction protein and to determine the interaction region between PKM2 and USP4. Immunofluorescence was performed to determine the cellular localization of USP4 and PKM2. The regulation of PKM2 by USP4 was examined by western blot and ubiquitination assay. MTT assays, glucose uptake, and lactate production were performed to analyze the biological effects of USP4 in gastric cancer cells. Results USP4 interacts with PKM2 and catalyzes the de-ubiquitination of PKM2. Overexpression of USP4 promotes cell proliferation, glucose uptake, and lactate production in gastric cancer cells. Knockdown of USP4 reduces PKM2 levels and results in a reduction in cell proliferation and the glycolysis rate. Conclusions USP4 plays a tumor-promoting role in gastric cancer cells by regulating PKM2.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0290688