Identification of the novel ASC-binding molecules as therapy targets for advanced colon cancer

结直肠癌的复发率很高，在日本是第二大死亡原因。ASC是一种形成多种炎症体的适配蛋白，在天然免疫细胞中对caspase-1的激活和IL-1b、IL-18的分泌起着至关重要的作用。ASC也被报道为几种人类癌症的表观遗传沉默基因，包括结肠癌。然而，有关ASC在肿瘤细胞中调控的信号通路的信息却很少。在这里，为了研究ASC在癌症进展中的作用，我们在两个癌细胞系中过表达ASC。在ASC表达的细胞中，细胞增殖受到抑制。利用功能蛋白质组方法，我们鉴定了几个与信号转导、细胞周期和细胞凋亡有关的候选蛋白质。我们的结果提示，ASC可能通过调节几个信号通路来抑制癌细胞的增殖。

Colorectal cancers have high rate of recurrence and is the second leading cause of death in Japan. ASC is an adaptor protein to form various inflammasomes, and has a crucial role for caspase-1 activation and secretion of IL-1b and IL-18 in innate immune cells. ASC has been also reported as an epigenetically silenced gene in several human cancers, including colon cancers. However, 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, we overexpressed ASC in two cancer cell lines. The cell proliferation was attenuated in ASC expressed cells. Using functional proteome approaches, we identified several candidate proteins involved in signal transduction, cell cycle, and apoptosis. Our results suggested that ASC might contribute to the suppression of cancer cell proliferation through a modulation of several signaling pathways.