肝转移是结直肠癌致死的主要原因，但机制不清。目前研究表明肿瘤酸性微环境促进肿瘤细胞的侵袭转移。本课题组前期研究发现，适应酸性环境的结直肠癌细胞侵袭能力增强，酸敏感离子通道蛋白ASIC2a表达上调，且细胞核内转录因子NFAT1增加；敲低ASIC2a显著抑制其侵袭，并减少NFAT1入核；我们还初步观察到ASIC2a在临床结直肠癌标本及肝转移灶中高表达。据此我们推测：酸性环境下ASIC2a通过激活NFAT1而参与调节结直肠癌肝转移。本项目拟以结直肠癌组织样本为研究对象，观察ASIC2a在结直肠癌原发灶及转移灶中的表达，并分析它的表达与临床病理特征的关系；在此基础上，进一步在细胞和分子水平上分析ASIC2a及其下游分子NFAT1与肝转移生物学行为的关系。本研究拟在组织、动物、细胞和分子水平系统阐述酸性环境下ASIC2a对结直肠癌转移的作用及分子机制，为结直肠癌肝转移的诊断和治疗提供新靶点。

Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC), with the underlying mechanism poorly known. It has been reported that acidic tumor microenvironment promotes metastasis of cancer cells. Our preliminary study showed that the increased invasion capacity of acidosis-adapted CRC cells was accompanied with up-regulation of acid sensing ion channel ASIC2a. Knock-down of ASIC2a attenuated the invasion capacity and nucleus translocation of transcription factor NFAT1 of acidosis-adapted CRC cells. Also, the high expression of ASIC2a was found in CRC tissue and liver metastatic foci. Therefore, we hypothesize that ASIC2a promotes liver metastasis of CRC cells under acidic microenvironment via activation of NFAT1. The expression of ASIC2a in primary colorectal cancer tissue and metastatic foci and the correlation between expression of ASIC2a and clinicopathological features would be determined. Furthermore, a series of methods will be applied to explore the role and underlying mechanism of ASIC2a in liver metastasis of CRC cells. The results might provide new target for the diagnosis and treatment of colorectal liver metastasis.