2. Academic Validation
  3. Prohibitin 2 confers NADPH oxidase 1-mediated cytosolic oxidative signaling to promote gastric cancer progression by ERK activation

Prohibitin 2 confers NADPH oxidase 1-mediated cytosolic oxidative signaling to promote gastric cancer progression by ERK activation

  • Free Radic Biol Med. 2024 Aug 23:224:130-143. doi: 10.1016/j.freeradbiomed.2024.08.028.
Liang Xu 1,  Li Meng 2,  Wanying Xiang 3,  Xinyue Wang 3,  Jiezhen Yang 4,  Chang Shu 3,  Xiao Hong Zhao 5,  Ziye Rong 6,  Yan Ye 7
Affiliations

Affiliations

  • 1 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China; School of Biomedical Sciences and Pharmacy, The University of Newcastle, NSW, 2308, Australia.
  • 2 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China; Department of Prenatal Diagnostic Center, People's Hospital of Puyang, Puyang, 457001, China.
  • 3 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
  • 4 Department of Pathology, Zhongshan Hospital (Xiamen Branch), Fudan University, Xiamen, 361015, China.
  • 5 School of Biomedical Sciences and Pharmacy, The University of Newcastle, NSW, 2308, Australia.
  • 6 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. Electronic address: 2021500003@ahmu.edu.cn.
  • 7 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. Electronic address: yeyan@ahmu.edu.cn.
PMID: 39182738 DOI: 10.1016/j.freeradbiomed.2024.08.028
Abstract

Oxidative signaling plays a dual role in tumor initiation and progression to malignancy; however, the regulatory mechanisms of oxidative stress in gastric Cancer remain to be explored. In this study, we discovered that Prohibitin 2 (PHB2) specifically regulates cytosolic Reactive Oxygen Species production in gastric Cancer and facilitates its malignant progression. Previously, we found that PHB2 is upregulated in gastric Cancer, correlating with increased tumorigenicity of gastric Cancer cells and poor patient prognosis. Here, we discovered that PHB2 expression correlates with the activation of the ERK/MAPK cascade, positively regulating the top gene NADPH Oxidase 1 (NOX1) within this pathway. Further mechanistic investigation reveals that PHB2 enhances NOX1 transcription by interacting with the transcription factor C/EBP-beta and promoting its translocation into the nucleus, resulting in elevated intracellular oxidative signaling driven by NOX1, which subsequently activates ERK. Therefore, we propose that targeting PHB2-C/EBP-beta-NOX1-mediated cytosolic oxidative stress could offer a promising therapeutic avenue for combating gastric Cancer malignant progression.

Keywords

ERK; Gastric cancer; NOX1; Oxidative signaling; PHB2.

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