Enzyme ‘Snitches’ On Cancer Cells To The Immune System

By cutting DNA in the nucleus of a cancer cell, the enzyme MUS81 reveals their location to immune cells, triggering an attack.

AsianScientist (May 19, 2016) – Researchers in Singapore have identified an enzyme that acts as a ‘snitch’, revealing cancer cells to the immune system. Their work was published in Immunity.

The conventional wisdom about cancer cells is that they are masters of camouflage, invisible to the immune system. However, occasionally, the immune system is alerted to the presence of a cancer cell and springs into action to attack it.

The present study, led by Assistant Professor Stephan Gasser from the National University of Singapore’s Yong Loo Lin School of Medicine, found that when an enzyme called MUS81 cuts DNA in the nucleus, the DNA is not degraded but rather moves to the cytoplasm in cancer cells. DNA being in the wrong place alerts the immune system, triggering it to attack cancer cells.

First author Dr. Samantha Ho and colleagues found that out-of-place DNA in cancer cells activates the immune system by producing a substance called interferon, that subsequently activates immune cells called macrophages and T cells to kill cancer cells. MUS81 plays an essential role in this killing of cancer cells because nuclear DNA was not cut in cancer cells that lacked the enzyme and no activation of the immune system was observed in these cells.

Although most of the work has been carried out using in vivo studies, Gasser has been collaborating with Dr. Joanne Ngeow at the National Cancer Center Singapore to characterize the process in different types of human tumors. Their preliminary findings indicate that MUS81-induced movement of DNA to the cytosol also occurs in human cancer cells, including prostate and breast cancer.

Discovering this process in cancer cells has wider implications: several of the current chemotherapies against cancer activate MUS81, and may therefore trigger a stronger immune response. These therapies could enhance the effects of cancer immunotherapies when used in combination, resulting in better health outcomes for cancer patients.

The article can be found at: Ho et al. (2016) The DNA Structure-Specific Endonuclease MUS81 Mediates DNA Sensor STING-Dependent Host Rejection of Prostate Cancer Cells.


Source: National University of Singapore.
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