PMID- 37071129 OWN - NLM STAT- MEDLINE DCOM- 20230802 LR - 20230802 IS - 1557-3125 (Electronic) IS - 1541-7786 (Linking) VI - 21 IP - 8 DP - 2023 Aug 1 TI - Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation. PG - 825-835 LID - 10.1158/1541-7786.MCR-22-0814 [doi] AB - 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. IMPLICATIONS: By transcriptional upregulation of 6PGD, TAp73 promotes the generation of Ru5P and NADPH, and enhances tumor cell proliferation. CI - (c)2023 American Association for Cancer Research. FAU - Qiao, Rui AU - Qiao R AUID- ORCID: 0009-0000-9483-4871 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Wei, Mengmeng AU - Wei M AUID- ORCID: 0000-0002-7354-8304 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Chen, Hui AU - Chen H AUID- ORCID: 0009-0005-5767-0501 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Zhang, Xianhong AU - Zhang X AUID- ORCID: 0000-0002-8574-4951 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Zhang, Jie AU - Zhang J AUID- ORCID: 0009-0009-8135-6917 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Gao, Liyang AU - Gao L AUID- ORCID: 0000-0002-1362-6403 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Ma, Haijun AU - Ma H AUID- ORCID: 0009-0007-1247-6670 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Wang, Yujiong AU - Wang Y AUID- ORCID: 0000-0003-2522-3043 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. FAU - Li, Le AU - Li L AUID- ORCID: 0000-0003-3849-4854 AD - School of Life Sciences, Ningxia University, Yinchuan, China. AD - Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Yinchuan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cancer Res JT - Molecular cancer research : MCR JID - 101150042 RN - EC 1.1.1.43 (Phosphogluconate Dehydrogenase) RN - 53-59-8 (NADP) RN - 0 (Reactive Oxygen Species) SB - IM MH - Humans MH - *Phosphogluconate Dehydrogenase/genetics/metabolism MH - NADP/metabolism MH - *Neoplasms/pathology MH - Cell Proliferation MH - Reactive Oxygen Species/metabolism MH - Pentose Phosphate Pathway EDAT- 2023/04/19 06:00 MHDA- 2023/08/02 06:42 CRDT- 2023/04/18 11:13 PHST- 2022/10/15 00:00 [received] PHST- 2023/02/21 00:00 [revised] PHST- 2023/04/14 00:00 [accepted] PHST- 2023/08/02 06:42 [medline] PHST- 2023/04/19 06:00 [pubmed] PHST- 2023/04/18 11:13 [entrez] AID - 725940 [pii] AID - 10.1158/1541-7786.MCR-22-0814 [doi] PST - ppublish SO - Mol Cancer Res. 2023 Aug 1;21(8):825-835. doi: 10.1158/1541-7786.MCR-22-0814.