MUC1 and colorectal cancer pathophysiology considerations.
Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and co-investigators showed recently that MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through beta-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-beta-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.
Niv
Yaron
Y
Department of Gastroenterology, Rabin Medical Center, Petach Tikva 49100, Israel. yniv@clalit.org.il
D015820:Cadherins / Q000096:biosynthesis; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D005762:Gastroenterology / Q000379:methods; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008495:Medical Oncology / Q000379:methods; D008954:Models, Biological; D018396:Mucin-1 / Q000096:biosynthesis*; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D008024:Ligands; D018396:Mucin-1; D051176:beta Catenin