Mucin-4

Definition:

Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces. These glycoproteins play important roles in the protection of the epithelium and are implicated in epithelial renewal and differentiation. Regulates cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and its ability to act as an intramembrane ligand for ERBB2. Plays an important role in proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. In polarized epithelial cells, segregates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. Its ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation.

References:

[1]. Jin Zhang, et al. MUC4 expression and localization in gastrointestinal tract and skin of human embryos. Tissue Cell. 2006 Aug;38(4):271-5. [Content Brief]

[2]. N Moniaux, et al. Alternative splicing generates a family of putative secreted and membrane-associated MUC4 mucins. Eur J Biochem. 2000 Jul;267(14):4536-44. [Content Brief]

[3]. M Saitou, et al. MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas. J Clin Pathol. 2005 Aug;58(8):845-52. [Content Brief]

[4]. Kermit L Carraway, et al. Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive. Prog Nucleic Acid Res Mol Biol. 2002;71:149-85. [Content Brief]

[5]. Aydanur Karg, et al. MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in non-small cell lung cancer (NSCLC). Pathol Res Pract. 2006;202(8):577-83. [Content Brief]

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