According to a study published yesterday in The Journal of Clinical Investigation, researchers at the University of Pittsburgh Cancer Institute (UPCI) have determined the oncoprotein that allows a common and usually harmless virus to change healthy cells into a rare but deadly skin cancer called Merkel Cell Carcinoma (MCC). The result of the study could improve the diagnosis for MCC (Merkel Cell Carcinoma) and help to understand the development of other cancers.

Three years ago, UPCI’s researchers Yuan Chang, M.D., and Patrick S. Moore, M.D., M.P.H. discovered a new human cancer virus called Merkel Cell polyomavirus (MCV) in the University’s Cancer Virology Program. Until now it was unclear how the virus, which is responsible for the majority of MCC cases, triggered the development of cancer.

In order to establish this, the research team led by Masahiro Shuda, Ph.D. and UPCI research associate, systematically evaluated the viral proteins that might trigger the development of cancer cell growth. After establishing human MCC cell lines, the researchers discovered, that the cancer cells stopped replicating by knocking out a viral protein called “small tumor protein” (sT). Their research revealed that when they introduced sT into healthy cells in the lab, the cells took on the characteristics of cancer cells.

Dr. Shuda said,

“This was a surprise because the viral sT proteins from other similar viruses that cause cancers in laboratory animals do not directly increase cancer activity in cells. Once we found this, we had to next understand the biological mechanisms that make MCV sT a cancer-causing protein, or oncoprotein.”

Dr. Moore explained, that the Merkel Cell polyomavirus sT triggers a cellular process called “cap-dependent translation” that allows certain cellular oncoproteins to be produced.

Even though cancers caused by MCV are rare, the virus is important in helping scientists to identify cell pathways that are key to more common types of cancer which may also activate cap-dependant translation through DNA mutations rather than through virus infections.

Related studies recently published by the team in Emerging Infectious Diseases, revealed that four out of five healthy adults are generally infected by MCV. The virus resides in skin cells without causing any symptoms but has the potential to cause cancer if specific mutations occur in the virus’ DNA, for example, by ultraviolet light exposure. Researchers are currently investigating to identify new agents to target MCC cancer cells that may be more active and less toxic.

Scientists have recently discovered six other polyomaviruses as inapparent infections of people in addition to MCV, which is the first virus in the family of polyomaviruses that can cause human cancer. They are actively trying to establish whether these viruses are also causing cancer.

MCV is the Chang-Moore laboratory’s second human cancer virus discovery, the first one being the virus causing Kaposi’s carcome, the most common cancer among AIDS patients.

Dr. Chang, an American Cancer Society Professor of pathology, and Dr. Moore, an American Cancer Society Professor of microbiology and molecular genetics at the Pitt School of Medicine, led the study. Hyun Jin Kwun, Ph.D., and Huichen Fung, Ph.D., both of the Cancer Virology Program are co-authors of the study. The National Institutes of Health, the American Cancer Society and UPCI provided funding.

Written by Petra Rattue