Notum在胃肠道肿瘤发生、发展中的作用机制及临床转化前景OA

Gastrointestinal tumors are among the most prevalent malignant tumors worldwide,and their high incidence and mortality rates pose a serious threat to human health.Currently,early screening strategies for gastrointestinal cancers remain limited.Endoscopic examination is relatively invasive,while conventional tumor biomarkers such as carcinoembryonic antigen(CEA)have limited specificity and are insufficient for early and precise tumor identification when used alone.Therefore,novel molecular targets with dual potential for early diagnosis and targeted therapy are urgently needed.Palmitoleoyl-protein carboxylesterase(Notum)is a key endogenous negative regulator of the Wnt/β-catenin signaling pathway.Recent studies have demonstrated that Notum regulates multiple critical signaling pathways,including phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)and transforming growth factor-beta(TGF-β)signaling pathways,and is extensively involved in biological processes associated with gastrointestinal tumor progression,including tumor cell proliferation and invasion,maintenance of cancer stem cell properties,chemotherapy resistance,and remodeling of the immunosuppressive tumor microenvironment.This review systematically summarizes the molecular characteristics and biological functions of Notum,reviews its expression patterns and regulatory mechanisms in different gastrointestinal tumors,and discusses the controversies and challenges associated with its basic research and clinical translation.Furthermore,this review compares the common and tissue-specific roles of Notum in gastrointestinal tumors and proposes future research directions focusing on biomarker development and optimization of targeted therapeutic strategies.These findings may provide valuable insights for Notum-related basic research and the clinical translation of precision diagnosis and treatment strategies for gastrointestinal tumors.