Han JH, Lu KR, Zhang M, Gong GH. Pristimerin attenuates spasmolytic polypeptide-expressing metaplasia via p57 (Cdkn1c)-mediated glycolytic reprogramming: A metabolic avenue for gastric cancer prevention. World J Gastroenterol 2026; 32(32): 118600 [DOI: 10.3748/wjg.118600]
Corresponding Author of This Article
Guo-Hua Gong, PhD, Professor, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, No. 82 West College Road, Wenzhou 325035, Zhejiang Province, China. guohgong@wmu.edu.cn
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Oncology
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review-article
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Han JH, Lu KR, Zhang M, Gong GH. Pristimerin attenuates spasmolytic polypeptide-expressing metaplasia via p57 (Cdkn1c)-mediated glycolytic reprogramming: A metabolic avenue for gastric cancer prevention. World J Gastroenterol 2026; 32(32): 118600 [DOI: 10.3748/wjg.118600]
World J Gastroenterol. Aug 28, 2026; 32(32): 118600 Published online Aug 28, 2026. doi: 10.3748/wjg.118600
Pristimerin attenuates spasmolytic polypeptide-expressing metaplasia via p57 (Cdkn1c)-mediated glycolytic reprogramming: A metabolic avenue for gastric cancer prevention
Jun-Hao Han, Kong-Rui Lu, Min Zhang, Guo-Hua Gong
Jun-Hao Han, Kong-Rui Lu, Min Zhang, Guo-Hua Gong, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
Author contributions: Han JH wrote the manuscript; Zhang M and Lu KR designed the figure; Gong GH conceived the idea and revised the manuscript.
AI contribution statement: For the manuscript text, the author used DeepSeek to assist with language polishing and to screen for typos. The logical structure, main arguments, literature search, citation and figures, as well as the final version of the manuscript, were all completed independently by the author, who takes full responsibility for the content of this paper.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Guo-Hua Gong, PhD, Professor, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, No. 82 West College Road, Wenzhou 325035, Zhejiang Province, China. guohgong@wmu.edu.cn
Received: January 7, 2026 Revised: March 9, 2026 Accepted: May 28, 2026 Published online: August 28, 2026 Processing time: 207 Days and 13.8 Hours
Abstract
Gastric cancer is a malignancy with high mortality globally, and spasmolytic polypeptide-expressing metaplasia (SPEM), a critical precancerous lesion in gastric carcinogenesis, represents a crucial target for early intervention to halt malignant progression. Pristimerin is a natural triterpenoid compound that primarily induces apoptosis and cell cycle arrest, and inhibits tumor cell migration and invasion by suppressing signaling pathways, such as nuclear factor kappa-B, phosphatidylinositol 3-kinase/protein kinase B, and mitogen-activated protein kinase. This opinion review provides an in-depth understanding of recent studies, exploring the therapeutic effects of pristimerin on SPEM and its underlying molecular mechanism. A recent study innovatively revealed that pristimerin effectively reverses tamoxifen-induced damage to the gastric mucosa and the SPEM phenotype by modulating Cdkn1c (p57)-mediated glycolytic reprogramming. This finding not only offers a novel perspective on the role of metabolic reprogramming in precancerous gastric lesions but also highlights targeting the “p57-glycolysis” axis as a potential therapeutic strategy for preventing gastric cancer. As a naturally derived bioactive agent, pristimerin has promising potential for clinical translation.
Core Tip: This opinion review discusses evidence that the natural compound pristimerin reverses spasmolytic polypeptide-expressing metaplasia (SPEM) not only by alleviating high-dose tamoxifen-induced gastric mucosal injury and oxyntic atrophy, but also by restoring parietal and chief cell lineages and suppressing aberrant proliferation. The study further identifies Cdkn1c (p57) as a key metabolic checkpoint: p57 is downregulated during SPEM, upregulated following pristimerin treatment, and required for the compound’s antiglycolytic and anti-SPEM effects in gastric organoids.
