Abstract
Colorectal cancer (CRC), the third most common malignant tumor in the world, shows multiple complex and pathologies based on the impaired structure and function of the intestinal mucosal barrier. Goblet cells secrete mucins, which are involved in the formation of the intestinal mucosal barrier and not only lubricate and protect the intestinal mucosa but also participate in the processes of cell adhesion, intercellular signal transduction, and immune regulation. It is accepted that the disordered expression and dysfunction of mucins are associated with the occurrence and development of CRC. This article focuses on the secretory mucins encoded by a gene cluster located on chromosome 11p15.5 and systematically reviews their composition, regulation, function, and role in CRC, to deepen the understanding of the pathogeneses of CRC and to provide a new basis and ideas for the treatment of CRC.
Highlights
The incidence of colorectal cancers (CRCs) ranks third among common malignant tumors, and Colorectal cancer (CRC) has the second highest mortality (Bray et al, 2018)
It is accepted that the normal function of the intestinal mucosal barrier is important for maintaining digestion and absorption and preventing abnormal disease, while rupture and dysfunction of the intestinal mucosal barrier can lead to a series of pathophysiological changes in the intestinal mucosa and eventually cause the occurrence of malignant tumors and CRCs (Yu, 2018)
The current findings indicated the protective roles of MUC2 and MUC6 in the occurrence and development of CRC, while MUC5B was identified as a pathogenic factor
Summary
The incidence of colorectal cancers (CRCs) ranks third among common malignant tumors, and CRC has the second highest mortality (Bray et al, 2018). In addition to the HT29-5F12 clone, Leteurtre et al (2004) provided a mucus-secreting clone, HT29-5M21, which was composed of monolayered polar cells secreting mucus with strong antigastric mucin immunoreactivity, mainly expressing MUC5AC and MUC5B, and showing resistance to MTX and sensitivity to 5-FU, suggesting the different functions and chemotherapy sensitivities of MUCs. Unlike MUC2, the expression of MUC5AC can be found to different degrees during the development of CRC, both in mucinous and nonmucinous adenocarcinomas. In the intestinal cancer cell line LS180, the proinflammatory cytokines IL-6 triggered the expression of MUC2, MUC5B, and MUC6 genes, and promoted their secretion, whereas IL-1 or tumor necrosis factor-α (TNF-α) activated the expression of MUC2 and MUC5AC genes, and alteration of mucus layers was induced by these differentially expressed cytokines (Enss et al, 2000). They found that patients with deficient expression of the MUC6 gene showed short PFS, while patients with MUC6 overexpression had long PFS and cancer-specific survival (CSS), especially in stage II and III CRC, indicating the protective role of the MUC6 gene in the occurrence and development of CRC, which was related to favorable outcomes of CRC patients (Betge et al, 2016)
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