Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt

  Wilson, J.E., et al. Nature medicine 21, 906-913 (2015).

Speaker: Chu-Yi Hsieh(謝筑伊)                                           Time: 14:00~15:00, Jan. 6, 2015

Commentator: Professor Tzeng-Horng Leu (呂增宏老師)  Place: Room 601

Abstract:

Colon cancer is one of the leading causes of cancer-related death worldwide. There are several kinds of inflammasomes able to activate caspase-1, then leading the cleavage and release of interleukin-1β (IL-1β) and IL-18. The absent in melanoma 2 (AIM2) inflammasome is member of the HIN-200 family. It was originally proposed as a tumor suppressor gene in melanomas, and AIM2 mutations are found in human colorectal tumors. But the mechanism of AIM2 suppresses tumor growth remains unclear. The author used the azoxymethane/dextran sodium (AOM/DSS) model to study the role of AIM2 in colitis-associated cancer (CAC). They found that disease severity in Aim2-deficient mice was indistinguishable from that in wild-type controls. But Aim2^-/- had greater tumor load than Asc^-/- and Aim2^-/-/Apc^Min/+. The author also generated radiation bone marrow-chimeric mice, and found that Aim2 expression in non-bone marrow cells was primarily associated with the restriction of tumorigenesis during CAC. The author next examined the effect of AIM2 on the phosphatidylinositol3-kinase(PI3K)－Akt pathway of cellular which is frequently mutated inhuman colorectal cancer. The results showed that AIM2 restricted tumorigenesis via interacting with DNA-PK, which is a PI3K-related family member that promotes Akt phosphorylation, to regulate Akt activation. These findings suggest that Akt inhibitors could be used to treat AIM2-deficient human cancers.

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