{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMUC17 is a large, type I membrane-bound mucin primarily expressed in the gastrointestinal tract that plays an integral role in epithelial cell protection. Its structure comprises a long extracellular domain heavily decorated with O‐glycans, a SEA module that is typically proteolytically cleaved, two epidermal growth factor–like (EGF-like) motifs, a single transmembrane domain, and a short cytoplasmic tail containing potential phosphorylation sites. Notably, MUC17 is located in a gene cluster with other membrane mucin genes (e.g., MUC3A, MUC3B, and MUC12), yet its tissue-specific expression and regulatory characteristics distinguish its unique functions in maintaining the luminal structure and signal transduction in normal intestinal epithelia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the intestinal epithelium, MUC17 contributes significantly to barrier integrity and cytoprotection. Its C-terminal region contains a PDZ-binding motif, enabling a robust interaction with the scaffolding protein PDZK1; this interaction is essential for proper apical localization and stabilization of the mucin on the brush border. Functional studies in enterocyte models have shown that appropriate post-translational modifications—such as complex-type N-glycosylation and phosphorylation of specific cytoplasmic residues—are critical for MUC17’s cell surface localization, endocytosis upon secretagogue stimulation, and the shedding of mucin-containing vesicles. These dynamically regulated processes likely contribute to the defense against bacterial adhesion and invasion, as evidenced by increased epithelial permeability and enhanced susceptibility to enteroinvasive pathogens when MUC17 levels are reduced."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMUC17 expression and function are further modulated in response to environmental and inflammatory stimuli. Comparative mucin gene profiling in various epithelia—including the laryngeal mucosa under reflux conditions and the intestinal response to enteropathogenic bacteria—highlights the complex regulation of mucin secretion and gene expression under stress. Moreover, in vitro studies have demonstrated that inflammatory cytokines can upregulate MUC17 levels while also triggering its redistribution along the apical membrane, suggesting that MUC17 not only forms a physical barrier but may also serve as a responsive element to changes in the mucosal microenvironment. Additionally, its expression in normal, inflamed, and neoplastic colon tissue underscores its importance in both homeostatic and pathological states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAltered MUC17 expression and its epigenetic regulation have been linked to several pathologic conditions, particularly in cancer. In pancreatic ductal adenocarcinoma and gastric cancer, for example, aberrant overexpression of MUC17 has been observed—with epigenetic factors such as DNA methylation, histone modifications, and microRNA regulation governing its transcriptional control. Hypoxic conditions within tumors further modulate MUC17 levels via HIF1α-dependent mechanisms, a process that may be impaired when CpG motifs within the hypoxia-responsive elements are hypermethylated. In non–small cell lung cancer, downregulation of MUC17 via promoter hypermethylation is associated with the acquisition of resistance to EGFR tyrosine kinase inhibitors, while in gliomas and mucinous ovarian carcinoma, genetic variations and mutations in MUC17 correlate with increased malignancy and poorer patient prognosis. These findings support MUC17’s potential utility as a prognostic biomarker and a therapeutic target in diverse cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James R Gum, Suzanne C Crawley, James W Hicks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MUC17, a novel membrane-tethered mucin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.2002.6475"}], "href": "https://doi.org/10.1006/bbrc.2002.6475"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11855812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11855812"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jenny J L Ho, Reena S Jaituni, Suzanne C Crawley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-glycosylation is required for the surface localization of MUC17 mucin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12888891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12888891"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nicolas Moniaux, Wade M Junker, Ajay P Singh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of human mucin MUC17. Complete coding sequence and organization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M600302200"}], "href": "https://doi.org/10.1074/jbc.M600302200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16737958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16737958"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Emily K Malmberg, Thaher Pelaseyed, Asa C Petersson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C-terminus of the transmembrane mucin MUC17 binds to the scaffold protein PDZK1 that stably localizes it to the enterocyte apical membrane in the small intestine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20071068"}], "href": "https://doi.org/10.1042/BJ20071068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17990980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17990980"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Silvia Resta-Lenert, Srustidhar Das, Surinder K Batra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muc17 protects intestinal epithelial cells from enteroinvasive E. coli infection by promoting epithelial barrier integrity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00138.2010"}], "href": "https://doi.org/10.1152/ajpgi.00138.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21393431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21393431"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Thaher Pelaseyed, Jenny K Gustafsson, Ida J Gustafsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carbachol-induced MUC17 endocytosis is concomitant with NHE3 internalization and CFTR membrane recruitment in enterocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00141.2013"}], "href": "https://doi.org/10.1152/ajpcell.00141.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23784542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23784542"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hannah Schneider, Evelin Berger, Brendan Dolan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human transmembrane mucin MUC17 responds to TNFα by increased presentation at the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20190180"}], "href": "https://doi.org/10.1042/BCJ20190180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31387973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31387973"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tina L Samuels, Ethan Handler, Michael L Syring, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Otol Rhinol Laryngol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/000348940811700911"}], "href": "https://doi.org/10.1177/000348940811700911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18834073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18834073"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mônica A M Vieira, Tânia A T Gomes, Antonio J P Ferreira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two atypical enteropathogenic Escherichia coli strains induce the production of secreted and membrane-bound mucins to benefit their own growth at the apical surface of human mucin-secreting intestinal HT29-MTX cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/IAI.01115-09"}], "href": "https://doi.org/10.1128/IAI.01115-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20065027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20065027"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ying Luu, Wade Junker, Satyanarayana Rachagani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human intestinal MUC17 mucin augments intestinal cell restitution and enhances healing of experimental colitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2010.03.001"}], "href": "https://doi.org/10.1016/j.biocel.2010.03.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20211273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20211273"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shantibhusan Senapati, Samuel B Ho, Poonam Sharma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of intestinal MUC17 membrane-bound mucin in inflammatory and neoplastic diseases of the colon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jcp.2010.078717"}], "href": "https://doi.org/10.1136/jcp.2010.078717"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20702471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20702471"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sho Kitamoto, Norishige Yamada, Seiya Yokoyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation and histone H3-K9 modifications contribute to MUC17 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwq155"}], "href": "https://doi.org/10.1093/glycob/cwq155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20926598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20926598"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0044108"}], "href": "https://doi.org/10.1371/journal.pone.0044108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22970168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22970168"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Bing Yang, Aiwen Wu, Yingqi Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mucin 17 inhibits the progression of human gastric cancer by limiting inflammatory responses through a MYH9-p53-RhoA regulatory feedback loop."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1279-8"}], "href": "https://doi.org/10.1186/s13046-019-1279-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31262330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31262330"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Shuye Lin, Hongyun Ruan, Lin Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acquired resistance to EGFR-TKIs in NSCLC mediates epigenetic downregulation of MUC17 by facilitating NF-κB activity via UHRF1/DNMT1 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.75963"}], "href": "https://doi.org/10.7150/ijbs.75963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36778111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36778111"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Ching-Wen Yang, Cherry Yin-Yi Chang, Ming-Tsung Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations of MUC17 are associated with endometriosis development and related infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-015-0209-7"}], "href": "https://doi.org/10.1186/s12881-015-0209-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26285705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26285705"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Gabriel Cardoso Machado, Valéria Pereira Ferrer "}, {"type": "b", "children": [{"type": "t", "text": "MUC17 mutations and methylation are associated with poor prognosis in adult-type diffuse glioma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2023.120762"}], "href": "https://doi.org/10.1016/j.jns.2023.120762"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37562166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37562166"}]}]}]}