Functional targeting of the MUC1 oncogene in human cancers

MUC1 has emerged as an especially attractive target for the development of anti-cancer agents. However, to date, there are no approved antibodies or small molecules that target MUC1. One reason is that historically much of the work on MUC1 focused on MUC1-N, the shed mucin component, and not MUC1-C, the transmembrane receptor subunit. Nonetheless, recent advances have provided new insights into: (i) the interactions of MUC1-C with diverse effectors, such as β-catenin, receptor tyrosine kinases, c-Src, c-Abl, p53, HSPs and galectin-3 among others, that have been linked to transformation; (ii) the function of MUC1-C and specifically the MUC1-C cytoplasmic domain in inducing transformation and the role of dominant-negative mutants in reversing the malignant phenotype; and (iii) the activation of gene signatures by MUC1-C that are predictive of clinical outcome in patients with carcinomas. Moreover, the demonstration that direct targeting of MUC1-C function blocks survival and tumorigenicity of human breast carcinoma cells indicates that MUC1-C is a druggable target that is of potential importance to cancer treatment. ©2009 Landes Bioscience.