Investigating the AIM2 Inflammasome Activation in Nasopharyngeal Carcinoma

Inflammation is a hallmark of cancer, especially in the infection-associated cancer. IL-1β, a major proinflammatory cytokine in tumor milieu, is regulated by inflammasome in response to pathogen and damage. Nasopharyngeal carcinoma (NPC) is a cancer prominent in Taiwanese population and is closely associated with Epstein-Barr virus (EBV) infection. We have examined the AIM2 inflammasome expression in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) tissues. We found that the AIM2 inflammasome is overexpressed in tumor cells and significantly correlated with better local-recurrence- and disease-free survival of NPC patients after treatment. In addition, the AIM2 inflammasomes was induced by dsDNA in NPC cells, which could be further enhanced by irradiation. However, the role of inflammasome activation in NPC is still unknown. Thus, we plan to investigate the AIM2 inflammasome activation in NPC in vitro and in vivo. The specific aims are as follows. (1) Uncovering the protein components of AIM2 inflammasome by the high-through proteomics approaches. The identification of the novel components may help us to understand the AIM2-mediated mechanism, and explore the AIM2 pathway in NPC; (2) Evaluating the mechanism of dsDNA-induced AIM2 activation in NPC cells in response to irradiation. (3) Establishing the role of AIM2 and its associated proteins in an in vivo mouse model. Our study may clarify the molecular mechanisms of AIM2 activation in vitro (NPC cells) and in vivo (mouse model). The findings may also open a new direction for future therapy or drug development for cancer through inflammation modulation.

Project ID:PC10202-0649
External Project ID:NSC101-2320-B182-010-MY3