School of Life Sciences, Ningxia University, Yinchuan, China.
Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China.
Mol Cancer Res. 2023 Aug 1;21(8):825-835. doi: 10.1158/1541-7786.MCR-22-0814.
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.
癌细胞经常改变代谢以支持生物发生和增殖，并在特定代谢应激下存活。葡萄糖相关的戊糖磷酸途径（PPP）对癌细胞增殖至关重要。特别是 PPP 中的第二个脱氢酶 6-磷酸葡萄糖酸脱氢酶（6PGD），催化 6-磷酸葡萄糖酸脱羧生成核酮糖 5-磷酸（Ru5P）。然而，控制癌细胞中 6PGD 表达的机制尚不清楚。在此，我们表明 TAp73 通过激活 6PGD 增加 Ru5P 和 NADPH 的产生，以抵消活性氧并保护细胞免于凋亡。此外，6PGD 的过表达挽救了 TAp73 缺陷细胞的增殖和致瘤能力。这些发现进一步确立了 TAp73 在葡萄糖代谢调节中的关键作用，表明 TAp73 可以激活 6PGD 表达以支持致癌细胞生长。
通过对 6PGD 的转录上调，TAp73 促进 Ru5P 和 NADPH 的生成，并增强肿瘤细胞的增殖。
