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

结直肠癌复发率高，是日本第二大死亡原因。ASC是形成多种炎性小体的适配蛋白，在先天免疫细胞中caspase-1激活和IL-1b、IL-18分泌中起着至关重要的作用。据报道，ASC在包括结肠癌在内的几种人类癌症中也是一种表观遗传沉默基因。然而，关于ASC在肿瘤细胞中调控的信号通路的信息很少。在这里，为了研究ASC在癌症进展中的作用，我们在两种癌细胞系中过表达ASC。表达ASC的细胞增殖能力减弱。利用功能蛋白质组学方法，我们确定了几个参与信号转导、细胞周期和凋亡的候选蛋白质。我们的研究结果表明，ASC可能通过调节几种信号通路来抑制癌细胞增殖。

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.