Investigating the Aim2 Inflammasome Activation in Nasopharyngeal Carcinoma

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 inhibited by caspase inhibitor. However, the role of inflammasome activation in NPC is still unknown. Based on the nature of NPC tumor and our preliminary results, we plan to 1) investigate if AIM2 plays a role in tumorigenesis by analyzed its functions in cell proliferation, cell migration and invasion as well as anchorage-independent growth in soft agar; 2) to establish the molecular mechanisms of AIM2 inflammasome by uncovering the AIM2 complex in NPC cells, with or without the dsDNA treatment by using 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; 3) to establish the role of AIM2 in the host-tumor cell interaction using an in vivo syngeneic mouse model. This may help us to clarify if AIM2-mediated IL-1 is involved in tumor growth and the animal survival after treatment. We also plan to determine the tumor-host cell interaction through analyzing infiltrated leukocytes and effector cells responsive to AIM2-mediated function in the mouse model. The new findings in this study may open a new direction for future therapy or drug development for cancer by inflammation modulation.

Project ID:PC10007-1169
External Project ID:NSC100-2320-B182-020