演題：The Viral Basis of Cancer
 
演者：Prof. David T. Ting, MD　
(Scientific Director, Mass General Brigham Cancer Institute, Zebunisha Juma Endowed Chair, Harvard Medical School, USA)
 
Abstract：
The aberrant expression of repeat elements is a common feature found in pancreatic ductal adenocarcinoma (PDAC). The majority of these are non-coding RNAs that have shown the ability to stimulate a viral-like innate immune response. We have identified the association and functional effect of repeat RNAs in human PDAC tumors with single molecular imaging revealing the dysregulation of cell state in PDAC cells and cancer associated fibroblasts (CAFs). In addition, we find that PDAC cells utilize the long interspersed nuclear element 1 (LINE-1) retrotransposon as a mechanism to tolerate high viral repeat responses. LINE-1 suppression significantly inhibited PDAC tumor growth both in vitro and in vivo. Total RNA sequencing revealed high enrichment of innate immune response-related pathways including IL6-JAK-STAT3 signaling, inflammatory response, interferon response, and apoptosis in LINE-1 knockdown PDAC cell lines. These immune related pathways are suppressed by deletion of RIG-I and MAVS, two components of viral RNA sensing. Mechanistically, we demonstrated that LINE-1 is associated with repeat RNAs with the MOV10 RNA helicase to process repeat RNAs. Altogether these results demonstrate PDAC utilization of viral mimicry mechanisms to induce a pro-tumoral inflammatory response, which offers a novel therapeutic target to re-activate innate immunity.
 
日　時：２０２６年７月３０日(木)　１７:００〜１８:００
場　所：吉田記念講堂