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Supplementary Figure 1 from Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation

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posted on 2023-08-01, 08:43 authored by Rui Qiao, Mengmeng Wei, Hui Chen, Xianhong Zhang, Jie Zhang, Liyang Gao, Haijun Ma, Yujiong Wang, Le Li

S1. TAp73 activates the expression of 6PGD

Funding

Natural Science Foundation of Ningxia Province (Natural Science Foundation of Ningxia)

CAST Innovation Foundation

National Natural Science Foundation of China (NSFC)

Ningxia University

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ARTICLE ABSTRACT

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.

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    Molecular Cancer Research

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