MUC13

Official Full Name

mucin 13, cell surface associated

Organism

Homo sapiens

GeneID

56667

Background

Epithelial mucins, such as MUC13, are a family of secreted and cell surface glycoproteins expressed by ductal and glandular epithelial tissues (Williams et al., 2001 [PubMed 11278439]).[supplied by OMIM, Jul 2008]

Synonyms

DRCC1; MUC-13;

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Detailed Information

Mucin13 (MUC13) encodes a membrane-bound mucin that is involved in the development of tumors by regulating a variety of signaling pathways, and is important for early diagnosis and clinical treatment of patients. MUC13 is normally localized to the apical membrane surface of epithelial cells of organs such as the large intestine, trachea, kidney, small intestine, stomach and esophagus. It also detects the expression of MUC13 on hematopoietic cells, middle ear cells, conjunctival epithelial cells, and testicular epithelial cells. The MUC13 protein consists of two different subunits, α and β, and contains an N-terminal signal peptide, a tandem repeat (TR) domain, and a sea urchin sperm protein enterokinase and agrin (SEA) domain. An epidermal growth factor (EGF)-like domain, a single-stranded transmembrane (TM) domain, and a cytoplasmic tail domain, and a plurality of different functional domains.

Figure 1. Schematic representation showing the overall mechanism of MUC13 in modulating glucose metabolic network and driving tumorigenic microenvironment. (Kumari, S., et al. 2018)

Cancer Promoting Mechanism of MUC13

MUC13 promotes NF-κB activation by interacting with tumor necrosis factor (TNF) receptor and E3 ligase cIAP1 in colorectal cancer, increasing receptor-interacting serine/threonine protein kinase 1 Ubiquitination. MUC13 increases the ataxia telangiectasia-mutated gene (ATM) phosphorylation and ubiquitination of NF-κB modulators to promote NF-κB activation to up-regulate BCL-XL expression. MUC13 promotes the growth and survival of cancer cells by activating the NF-κB pathway in renal cancer cells and induces BCL-XL expression to inhibit apoptosis. MUC13 also enhances the response of NF-κB signaling to TNF and DNA damaging agents, providing a new molecular target for specific inhibition of NF-κB activation.

MUC13 has the ability to promote migration and invasion of a variety of tumor cells. Overexpression of MUC13 promotes skeletal remodeling and cell migration and invasion of ovarian cancer cells SKOV-3 by activating human epidermal growth factor receptor 2 (HER-2) and p21-activated kinase 1 (PAK1). S.KHAN et al. found that MUC13 induces activation of HER-2 and its downstream mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and adhesion plaque kinase (FAK) to promote cytoskeletal remodeling, cell invasion and migration of pancreatic ductal adenocarcinoma cells.

MUC13 and Tumor

The transcription and protein expression of MUC13 in various malignant tumor tissues was significantly higher than that in adjacent tissues. The study examined the expression of MUC13 protein in 114 patients with gastric cancer by immunohistochemistry (IHC). The results showed that significant and diffuse cytoplasmic staining was observed in 64.9% of cancer tissues, and the expression level of MUC13 was correlated with gastric cancer. T and N stages are irrelevant and are associated with intestinal type gastric cancer (Lauren type). The study found that MUC13 is expressed only on the surface of the apical membrane in normal colorectal tissues, while MUC13 is highly expressed in the cytoplasm in poorly differentiated and advanced colorectal cancer tissues, and its expression level is independent of tumor location, size and TNM stage. Silencing MUC13 promotes the chemosensitivity of colorectal cancer cells to cytotoxic drugs and inflammatory factors, eliminates the enrichment of CD133+ and CD44+ cancer stem cells induced by chemotherapy, and slows the growth of xenograft tumors in nude mice. In addition, silencing of MUC13 in combination with 5 fluorouracil induced tumor regression.

References:

Sheng, Y. H. , He, Y. , Hasnain, S. Z. , Wang, R. , & Mcguckin, M. A. . (2016). Muc13 protects colorectal cancer cells from death by activating the nf-κb pathway and is a potential therapeutic target. Oncogene, 36(5), 700-713.
Kumari, S. , Khan, S. , Gupta, S. C. , Kashyap, V. K. , Yallapu, M. M. , & Chauhan, S. C. , et al. (2018). Muc13 contributes to rewiring of glucose metabolism in pancreatic cancer. Oncogenesis, 7(2), 19.
Khan, S. , Sikander, M. , Ebeling, M. C. , Ganju, A. , Kumari, S. , & Yallapu, M. M. , et al. (2016). Muc13 interaction with receptor tyrosine kinase her2 drives pancreatic ductal adenocarcinoma progression. Oncogene.

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