Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation.

Rui Qiao, Mengmeng Wei, Hui Chen, Xianhong Zhang, Jie Zhang, Liyang Gao, Haijun Ma, Yujiong Wang, Le Li

Molecular cancer research : MCR 2023 Aug 01

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Cancer cells frequently alter their metabolism to support biogenesis and proliferation and survive specific metabolic stressors. The glucose-associated pentose phosphate pathway (PPP) is crucial for cancer cell proliferation. In particular, 6-phosphogluconate dehydrogenase (6PGD), the second dehydrogenase in the PPP, catalyzes the decarboxylation of 6-phosphogluconate into ribulose 5-phosphate (Ru5P). However, the mechanisms controlling 6PGD expression in cancer cells remain unclear. Herein, we show that TAp73 increases Ru5P and NADPH production through 6PGD activation to counteract reactive oxygen species and protects cells from apoptosis. Moreover, 6PGD overexpression rescues the proliferation and tumorigenic ability of TAp73-deficient cells. These findings further establish the critical role of TAp73 on glucose metabolism regulation, demonstrating that TAp73 can activate 6PGD expression to support oncogenic cell growth. By transcriptional upregulation of 6PGD, TAp73 promotes the generation of Ru5P and NADPH, and enhances tumor cell proliferation. ©2023 American Association for Cancer Research.

Citation

Rui Qiao, Mengmeng Wei, Hui Chen, Xianhong Zhang, Jie Zhang, Liyang Gao, Haijun Ma, Yujiong Wang, Le Li. Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation. Molecular cancer research : MCR. 2023 Aug 01;21(8):825-835