Understanding Cellular Transformation by Merkel Cell Polyomavirus
Vadim Molla, Christian Berrios, Esther Park, James A. DeCaprio, M.D.
Dana Farber, CanCure
Motivation: Merkel cell polyomavirus is a virus whose proteins are able to turn into oncogenic drivers and induce cellular proliferation and transformation. The study of these proteins is essential to a better understanding of the development and sustainability of Merkel cell cancer by taking a closer look at two phenotypes induced by the presence of the viral proteins on cellular MCT1 and P53.
Problem: Merkel cell virus proteins are shown to increase the presence of MCT1, a protein suspected to import lactate into the cell. This is a strange phenomenon when considering that cancer cells traditionally export lactate for the sake of inflammation. The results of this work investigate the importance of this protein to the cell and seek to determine how it is regulated by the Merkel cell virus proteins to ultimately ask as to whether this is necessary for transformation.
One of the hallmarks of cancer is the avoidance of cell apoptosis, most often done by suppression of P53, a protein that intimately involved in programmed cell death. Merkel cell viral proteins are not shown to interact with P53 directly, as evidenced by the presence of wildtype P53 in the majority of Merkel cell cancer tumors. The mechanism of the suppression of P53 is important across all types of cancer.
Results: Using mRNA protein analysis, and immuno-florescent imaging, the presence of MCT1 was determined to indeed be increased at an mRNA and protein level. MCT1 inhibition was also shown to decrease cell viability. P53 was shown not to associate with the Merkel cell viral proteins via MUDPIT analysis but the presence of other proteins were seen and will further be investigated.
Conclusion: A possible pathway for MCT1 regulation has been suggested due to the evidence presented. New protein associations with P53 were also seen via the techniques used and offer insight to how P53 is bypassed in the transformation of Merkel cells.