Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Potential involvement of ASC in cancer progression and metastasis. (#164)

Chifumi Fujii 1 , Shigeaki Hida 2 , Kensuke Ito 2 , Masato Kitazawa 2 , Shun'ichiro Taniguchi 2
  1. Development of Integrative Physiology & Bio-System Control, Shinshu University Graduate School of Medicine, Matsumoto city, Nagano, Japan
  2. Department of Molecular Oncology, Shinshu University Graduate School of Medicine, Matsumoto city, Nagano, Japan

Apoptosis-associated spec-like protein containing a caspase recruitment domain (ASC), found in our lab, is an adaptor protein that is a main mediator to form various inflammasomes, and has a crucial role such as maturation of interleukin (IL)-1 and IL-18 by activating caspase-1. ASC has been also known as a pro-apoptotic molecule that is epigenetically silenced in several human cancers, including melanoma, during their progression. Although they are well-known phenomena, little information is available for the signaling pathway regulated by ASC in tumor cells. Here, in order to investigate the roles of ASC in cancer progression, i.e. acquisition of metastatic ability of cancer cells, we used several cell lines with differential endogenous expression of ASC. In particular, we artificially overexpressed ASC in HT1080 cell line, where ASC is epigenetically suppressed, and/or ablated ASC mRNA by RNA interference in three melanoma cell lines expressing ASC. The retroviral reconstitution of ASC suppressed cellular proliferation and tumorigenesis of HT1080 in the xenograft model. When we did ASC knockdown in two human and one murine melanoma cell lines, the enhancement of snail mRNA expression was observed. Furthermore, endogenous snail mRNA expression levels were inversely correlated with ASC expression between two human melanoma cell lines. Snail has been reported as a key molecule of epithelial-mesenchymal transition (EMT). Recent evidence has highlighted a link between EMT and the cancer stem cells that initiate and maintain tumors, and EMT has also been implicated in invasion and metastasis. Our findings suggested that a potential involvement of ASC in cancer progression and metastasis by the regulation of snail expression level. Further analyses remain to be done to clarify the roles of ASC in metastasis more in detail, trying to examine the effect of ASC on metastatic potential with animal models.