Open Access

ARTICLE

CENPF Promotes Gastric Cancer Proliferation through c-Myc-Mediated GLS1 Upregulation and Glutamine Metabolism

Min Dong^1,#, Zongchang Song^2,#, Xiaohui Lu^1,3,#, Minxue Lu^4,*, Chen Zhong^1,*

1 Department of Oncology, No. 960 Hospital of PLA, Jinan, China
2 Department of Oncology, Shanghai University Affiliated Mengchao Cancer Hospital, Shanghai, China
3 Department of Oncology, The Postgraduate Training Base of Jinzhou Medical University (No. 960 Hospital of PLA), Jinan, China
4 Department of Gastroenterology, Huzhou College Affiliated Nantaihu Hospital, Huzhou, China

* Corresponding Authors: Minxue Lu. Email: ; Chen Zhong. Email:
# These authors contributed equally to this work as the first author

(This article belongs to the Special Issue: Microenvironment, Microbiota and Immune System in Digestive Cancers)

Oncology Research 2026, 34(3), 22 https://doi.org/10.32604/or.2026.068508

Received 30 May 2025; Accepted 25 December 2025; Issue published 24 February 2026

Abstract

Background: Gastric cancer (GC) remains highly lethal, with metabolic reprogramming as a key hallmark. This study explores Centromere Protein F (CENPF)’s role in GC pathogenesis, specifically its regulation of glutamine metabolism. Methods: The Cancer Genome Atlas–Stomach Adenocarcinoma (TCGA-STAD), GSE19826, and GSE27342 datasets were analyzed by bioinformatics to identify key candidate genes in GC. The function of CENPF was assessed by flow cytometry, colony formation assays, and Cell Counting Kit-8 (CCK-8). RNA sequencing, metabolic profiling, chromatin immunoprecipitation (ChIP), western blot (WB), and luciferase reporter assay were employed to investigate the fundamental mechanisms. Results: CENPF was upregulated in GC tumor samples and had a high diagnostic potential. CENPF knockdown declined cell proliferation, caused G2 arrest, and promoted apoptosis in GC cells. RNA sequencing revealed that CENPF was involved in glutamine metabolism. CENPF overexpression enhanced glutamine consumption and glutamate production, while glutamine deficiency reversed CENPF-mediated cell survival. CENPF stabilized cellular myelocytomatosis (c-Myc) by preventing proteasomal degradation, bound to the glutaminase (GLS) promoter, promoting glutamine metabolism. Overexpression of GLS or c-Myc rescued the CENPF knockdown’s inhibitory effect on GC cell growth. Conclusion: Our findings identify a new CENPF/c-Myc/GLS axis that affects glutamine metabolism and cell survival in GC, implying that CENPF might be a novel target for the treatment of GC.

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