03:19pm Thursday 14 December 2017

Sylvester Researcher Identifies Key Connection between Cellular Sensor and Colorectal Cancer

“The cellular sensor STING is frequently functionally suppressed in colorectal cancer,” said Glen N. Barber, Ph.D., holder of the Eugenia J. Dodson Chair in Cancer Research at Sylvester, and professor and Chair of the Department of Cell Biology. “We believe that these findings may also be relevant for leukemias and other types of cancer.”

A recent article in the journal Cell Reports by Barber and a team of research colleagues reported their finding that deregulation of the STING (for stimulator of interferon genes) pathway in tumors may prevent phagocytes (white blood cells) in the immune system from recognizing and destroying cancer cells. However, defective STING signaling may help explain why oncolytic therapies that use viruses to destroy tumor cells are effective.

“Usually, active STING signaling prevents viruses from replicating in normal cells, but since this pathway is commonly repressed in cancer cells, viruses are more readily able to replicate and ‘burst’ the cells,” said Barber, a Sylvester member who was the article’s corresponding author.

Barber’s co-authors of “Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates with Tumorigenesis” were Sylvester researchers Tianli Xia, Ph.D., who was first author, Hiroyasu Konno, Ph.D., and Jeonghyun Ahn, Ph.D.

“As part of our study, we created a STING diagnostic assay that could be used to look at clinical specimens,” Barber said. “We believe that STING activity may be a crucial indicator of whether a patient will respond to oncoviral therapy, and perhaps other therapies, as well as help predict outcomes.”

Barber was the author of a seminal 2008 study, published in the journal Nature, that identified a key role for STING in helping the body’s immune system fight off viral and bacterial infections. Since then, he has continued to study STING’s function and biological importance, including publishing three reports in 2014 in Nature Communications.

In December, the journal Nature Reviews also published a review by Barber entitled “STING: Infection, Inflammation, and Cancer.”

In that article, Barber noted the multiple roles of the STING signaling pathway in controlling the body’s immune response to invading microbes, stimulating cells to produce anti-viral and anti-bacterial proteins, as well as cytokines that attract pathogen-fighting T-cells.

“In general, a transient STING response is vital for fighting infections,” he said. “However, chronic STING stimulation is implicated in autoimmune diseases like arthritis or severe systemic lupus erythamatosus. The discovery of the STING-controlled innate immune pathway opens exciting possibilities for the development of novel immunization regimes, as well as therapies to treat autoinflammatory disease and cancer.”


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