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Multiple roles and mechanisms of MUC6 in cancer (Review)

Xin Luo,Xiao Fu,Ying Xiong,P. Xiao

Published 2025 in International Journal of Molecular Medicine

ABSTRACT

Mucin 6 (MUC6), primarily expressed in the gastrointestinal (GI) epithelium, is a member of the mucin family characterized by a protein backbone with extensive glycosylation, playing a crucial role in preserving epithelial barrier integrity. Accumulating evidence indicates that MUC6 glycosylation contributes significantly to cancer development, diagnosis, therapy and prognosis-particularly in GI malignancies such as gastric, pancreatic and colorectal cancers. In the present review, current findings on the multifaceted roles of MUC6 across various cancers were comprehensively summarize. For instance, loss of MUC6 expression is frequently associated with gastric cancer risk, while its upregulation may serve as a valuable biomarker in prostate cancer biopsy, aiding in early detection. Additionally, the identification of MUC6-Tn glycoforms offers promising avenues for novel therapeutic strategies. The distinctive tandem repeat polymorphisms within the MUC6 gene further suggest its potential utility in assessing cancer susceptibility based on allele length variation. These insights underscore the relevance of MUC6 in both mechanistic research and clinical oncology. Although preliminary data are encouraging, large-scale, multicenter studies are necessary to fully validate the clinical application of MUC6 as a biomarker for cancer staging and prognosis. Finally, the present review outlines future directions for exploring MUC6 in the context of cancer therapy development.

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