MUC6, a mucin-encoding gene, is mainly expressed in the gastric epithelium and duodenal Brunner's glands. The encoded MUC6 protein, as a core component of gastric gland mucin, is heavily glycosylated by unique O-glycans. It plays a crucial role in maintaining the integrity of the gastric mucus barrier, potentially interacting with TFF2 through non-covalent lectin interactions and disulfide bridges [2].

MUC6 has been associated with multiple diseases. In Alzheimer's disease, its VNTR repeat expansion may be linked to AD pathologic severity, especially tau proteinopathy, and might influence AP2A2 gene expression [1]. In cancer, MUC6 expression varies. For example, in gastric cancer, its down-regulation due to promoter methylation is related to cancer progression [4]. In invasive mucinous adenocarcinoma of the lung, MUC6 expression is a favorable prognostic biomarker, with MUC6-expressing cells showing lower proliferation, motility, and invasiveness [3]. In pancreatic cancer, co-expression of α4GnT (which synthesizes αGlcNAc for MUC6) and MUC6 suppresses malignancy [5]. Also, genetic variations in MUC6 may be related to hepatocellular carcinoma and its progression [6].

In conclusion, MUC6 is essential for maintaining the gastric mucus barrier. Its dysregulation is implicated in various diseases, including Alzheimer's disease and multiple cancers. Studies on MUC6 contribute to understanding disease mechanisms and may offer potential targets for diagnosis and treatment in these disease areas.

References:

1. Nelson, Peter T, Fardo, David W, Katsumata, Yuriko. . The MUC6/AP2A2 Locus and Its Relevance to Alzheimer's Disease: A Review. In Journal of neuropathology and experimental neurology, 79, 568-584. doi:10.1093/jnen/nlaa024. https://pubmed.ncbi.nlm.nih.gov/32357373/

2. Hoffmann, Werner. 2015. TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review). In International journal of oncology, 47, 806-16. doi:10.3892/ijo.2015.3090. https://pubmed.ncbi.nlm.nih.gov/26201258/

3. Yamanoi, Kazuhiro, Fujii, Chifumi, Yuzuriha, Hanae, Asamura, Hisao, Nakayama, Jun. 2022. MUC6 expression is a preferable prognostic marker for invasive mucinous adenocarcinoma of the lung. In Histochemistry and cell biology, 157, 671-684. doi:10.1007/s00418-022-02093-1. https://pubmed.ncbi.nlm.nih.gov/35353213/

4. Shi, Ding, Xi, Xiao-Xia. . Regulation of MUC6 Methylation Correlates with Progression of Gastric Cancer. In Yonsei medical journal, 62, 1005-1015. doi:10.3349/ymj.2021.62.11.1005. https://pubmed.ncbi.nlm.nih.gov/34672134/

5. Yuki, Atsuko, Fujii, Chifumi, Yamanoi, Kazuhiro, Kawakubo, Masatomo, Nakayama, Jun. 2021. Glycosylation of MUC6 by α1,4-linked N-acetylglucosamine enhances suppression of pancreatic cancer malignancy. In Cancer science, 113, 576-586. doi:10.1111/cas.15209. https://pubmed.ncbi.nlm.nih.gov/34808019/

6. Lee, Hsiang-Lin, Chien, Yi-Chung, Wang, Hsiang-Ling, Yang, Shun-Fa, Yu, Yung-Luen. 2022. Analysis of MUC6 Genetic Variants on the Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma. In Journal of Cancer, 13, 3251-3257. doi:10.7150/jca.75754. https://pubmed.ncbi.nlm.nih.gov/36118520/