Cmtm4 Deficiency Inhibits Helicobacter pylori-Induced Gastric Carcinogenesis
Yanfei Lang1,2, Xiurui Han1,2,3, Xin Liu1,2
1Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
Pathology International
|May 28, 2025
Summary
CMTM4 deficiency inhibits Helicobacter pylori-induced gastric cancer (GC) by downregulating the IL-17 signaling pathway. This finding suggests CMTM4 as a potential target for GC prevention.
Area of Science:
- Gastroenterology
- Oncology
- Immunology
Background:
- Helicobacter pylori infection is a primary cause of gastric cancer (GC).
- Interleukin-17 (IL-17) mediated inflammation is critical in H. pylori infection and gastric carcinogenesis.
- The role of CMTM4, an IL-17 receptor subunit, in GC development is not well understood.
Purpose of the Study:
- To investigate the role of CMTM4 in H. pylori-induced gastric carcinogenesis.
- To elucidate the underlying molecular mechanisms involving IL-17 signaling.
Main Methods:
- Utilized Cmtm4 knockout (KO) mice to study H. pylori infection.
- Analyzed GC development, pseudopyloric metaplasia, and DNA damage.
- Investigated the IL-17 signaling pathway, including IL-17RC, NF-κB, and NOX1 expression.
Main Results:
- Cmtm4 deficiency significantly inhibited GC development and pseudopyloric metaplasia.
- Reduced DNA damage in the gastric mucosa of Cmtm4 KO mice.
- CMTM4 deletion downregulated the IL-17 signaling pathway, suppressing IL-17RC, NF-κB activation, and NOX1 levels.
Conclusions:
- CMTM4 plays a crucial role in promoting H. pylori-induced gastric carcinogenesis.
- CMTM4 deletion suppresses GC and precancerous lesions via the IL-17RC/NF-κB/NOX1 pathway.
- Targeting CMTM4 may offer a novel strategy for early GC prevention.
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