Mucin 1 has been considered as an oncoprotein, because there is accumulating evidence which suggests its cancer-promoting function. It was reported that, interacted with Kruppel-like factor 4 (KLF4), a Mucin 1 C-terminal subunit (Mucin 1-C) occupies the PE21 element of the p53 gene promoter, which recruits histone deacetylases, and suppresses the transcription of the p53 gene. p53 is one of the representative tumor suppressor genes functioning in apoptosis, genomic stability and the inhibition of angiogenesis. It is a master guardian and executioner that surveys genetic damage and responds to it by arresting the cell cycle and facilitating DNA damage repair, or by induction of cell death when the genetic damage is severe. Mucin 1 activates anti-apoptotic protein Bcl-xL and attenuates the loss of mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-9 activation, leading to the failure of apoptosis induction. In response to DNA damage, the non-receptor c-Abl tyrosine kinase is translocated to the nucleus and induces apoptosis of the cells, but Mucin 1 protein attenuates this nuclear translocation. As stated above, Mucin 1 is a tremendous oncoprotein that destroys apoptosis execution pathways, one of the most important anti-cancer machines contained in the cells. The anti-apoptotic function of molecules confers cancer cells with resistance to genotoxic anticancer drugs. Mucin 1 may contribute to metastasis, as it was demonstrated in vitro that the Mucin 1 protein can bind to intercellular adhesion molecule-1 (ICAM-1), which facilitates adhesion of breast cancer cells to endothelial cells, leading to adhesion and subsequent migration through the vessel wall. Moreover, Mucin 1 could have some role in GC stem cells, as it acts as a growth factor receptor on undifferentiated human embryonic stem cells and is expressed in acute myeloid leukemia stem cells. Intriguingly, it is also known that Mucin 1 facilitates cancer cell survival under hypoxic and nutrient-deprived conditions by regulating glucose and lipid metabolism and the cellular energy state.
Saeki N, Sakamoto H, Yoshida T. Mucin 1 Gene (MUC1) and Gastric-Cancer Susceptibility. International Journal of Molecular Sciences. 2014;15(5):7958-7973.