Studies Provide Insights into STING Sensor’s Role in Inflammation-Driven Cancer

“The ability to turn on or off the sensor known as STING (for stimulator of interferon genes) has significant clinical implications for the control of auto-inflammatory diseases and cancer,” said Glen N. Barber, Ph.D., Chairman and Professor of the Department of Cell Biology, Eugenia J. Dodson Chair in Cancer Research, and Associate Director for Basic Research at Sylvester Comprehensive Cancer Center. “Our research provides fresh insight into the causes of inflammation-driven malignant disease and may provide a basis for therapeutic strategies to help prevent particular cancer types.”

Barber was the author of a seminal 2008 study that identified a key role for STING in helping the body’s immune system fight off viral infections. Since then, he has continued to study STING’s function and biological importance, including how this signaling molecule is controlled, with three new studies published in the journal Nature Communications this year.

“A transient STING response is vital for fighting off acute infections. STING does this by recognizing invading pathogens and stimulating the production of host defense proteins that prevent infection and that stimulate the adaptive immune response,” Barber said. “However, unless the STING molecule is deactivated, it can lead to lethal inflammatory disease and certain cancers, as we show in our recent report.”

Barber leads a Miller School research team that has been studying host defenses against viruses, bacteria and other pathogens. Cellular sensors like STING detect these invaders soon after entry by recognizing the nucleic acid that comprises the microbe’s genome. This activates signaling pathways that tell the cell to produce anti-viral and anti-bacterial proteins, as well as cytokines that attract pathogen-fighting T-cells that play a key role in the body’s immune counter response.

Barber’s most recent study, “Inflammation-driven carcinogenesis is mediated through STING,” was published on October 10 with Miller School co-authors Jeonghyun Ahn, Ph.D.; Tianli Xia, Ph.D.; Hiroyasu Konno Ph.D; Keiko Konno; and Phillip Ruiz, M.D.

That study used an experimental model to show that the presence of STING promoted carcinogen triggered skin cancer, while the absence of STING resulted in cancer resistance. “This is the first study to show that a prolonged STING response can actually play a role in the genesis of malignant disease,” Barber said. “Given this data, we are naturally interested in evaluating STING’s role in controlling other types of cancer, such as colon, liver, lung and breast cancer.”

Barber’s lab has also shown that chronic STING activity can lead to lethal inflammatory disease such as severe systemic lupus erythamatosus (SLE), as emphasized in a recent publication, “Intrinsic Self-DNA Triggers Inflammatory Disease Dependent on STING,” also with co-authors Jeonghyun Ahn, Ph.D., and Phillip Ruiz, M.D., which was published in the Journal of Immunology this September. As a consequence, the body has devised several strategies to prevent STING overactivity.

For example, earlier this year, Barber collaborated on two other studies published in Nature Communications. He was co-author of a study, “Primate-specific miR-576-3p sets host defense signalling threshold,” published in the journal’s September 18 issue. “This paper described a new mechanism devised by the cell to prevent STING from becoming too active,” he said.

In addition, Barber was co-author of “Nucleic acid sensing by T cells initiates Th2 cell differentiation,” a paper published in Nature Communications April 10 with several researchers from Japan. The study found that T-cells could sense the presence of DNA released from dead cells and respond by stimulating the body’s immune system.

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Healthcanal Staff
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