MUC1 is a heavily glycosylated transmembrane glycoprotein which is overexpressed and aberrantly glycosylated in most human carcinomas. MUC1 contains a large tandem repeat, a short transmembrane, and a small cytoplasmic tail. Both tandem repeat and the cytoplasmic tail have been proposed to have significant contributions to cellular behavior. In the present study, we have investigated the role of MUC1 in cancer progression. First, we have studied the role of MUC1 in oncogenesis during pancreatic cancer. Our studies have shown that during pancreatic cancer, MUC1 regulates expression of PDGFA, an important growth factor which causes proliferation and invasion of cancer cells. Moreover, we have shown that MUC1 regulates epithelial to mesenchymal transition during pancreatic cancer and thereby contributes to metastasis. Second, we have investigated the role of MUC1 in regulation of myeloid derived suppressor cells. We have shown that under cancer progression MUC1 regulates expansion and suppressive function of myeloid derived suppressor cells. Genetic knockout of this protein causes mice to be more susceptible to cancer growth due to increased myeloid derived suppressor cells function and expansion. Taken together, MUC1 plays a dual role in oncogenesis and cancer immunology.
