@article{TCR120226,
author = {Man Gao and Yixun Zhang and Wenjing Bao and Yilin Shi and Weiyi Chen and Yang Liu and Rumeng Wang and Ning Zhang and Lingli Zhang and Lizhou Jia},
title = {METTL17 promotes gastric cancer progression via inhibiting glycogen synthase kinase-3β to activate Wnt/β-catenin signaling},
journal = {Translational Cancer Research},
volume = {15},
number = {7},
year = {2026},
keywords = {},
abstract = {Background: Gastric cancer (GC) is a highly prevalent malignancy associated with extremely poor prognosis. METTL17, a mitochondrial protein belonging to the methyltransferase-like (METTL) family, has been shown to drive the progression of several cancers including colorectal and oral cancers, yet its role in GC remains unexplored. This study sought to characterize the expression profile, biological functions, and underlying regulatory mechanisms of METTL17 in GC.Methods: In this study, bioinformatics analysis, tissue microarray (TMA) immunohistochemistry (IHC), and Western blot were performed to determine the expression levels of METTL17 in GC cells and tissues and to assess its clinical relevance. In vitro and in vivo (BALB/c immunodeficient nude mice) functional assays were conducted to investigate the effects of METTL17 on the proliferation, migration, invasion, and tumorigenic potential of GC cells. Quantitative proteomics and Western blot were further applied to screen and validate the downstream signaling pathways regulated by METTL17.Results: METTL17 was significantly upregulated in GC and correlated with poor prognosis in affected patients. Functional assays demonstrated that knockdown of METTL17 suppressed the proliferation, migration, invasion, and in vivo tumorigenic capacity of GC cells, whereas overexpression of METTL17 yielded the opposite effects. Mechanistically, quantitative proteomic profiling and Western blot analysis showed that METTL17 negatively regulated glycogen synthase kinase-3β (GSK-3β) expression, thereby activating the Wnt/β-catenin signaling pathway.Conclusions: METTL17 activates the Wnt/β-catenin signaling pathway by inhibiting GSK-3β expression, thereby promoting the malignant progression of cancer. This suggests that METTL17 is a promising potential therapeutic target for GC.},
issn = {2219-6803}, url = {https://tcr.amegroups.org/article/view/120226}
}