肿瘤转移是导致肝癌患者预后不良和高死亡率的重要因素。由Warburg效应引起的肿瘤酸性微环境在肿瘤转移过程中发挥着关键作用。因此，深入阐明肿瘤酸性微环境影响肿瘤转移的机制，有助于开发肝癌治疗的新策略。在前期的预实验中，我们首次发现体外模拟肿瘤酸性微环境可增强肝癌细胞的抗失巢凋亡能力，而使用自噬抑制剂可有效阻断该作用。据此，我们假设肿瘤酸性微环境通过诱导自噬增强肝癌细胞的抗失巢凋亡能力，并最终促进肝癌转移。本课题计划利用HCC细胞模型、裸鼠肿瘤模型和肝癌临床样本研究肿瘤酸性微环境促进肿瘤转移的新机制，即通过诱导自噬促进肿瘤细胞抗失巢凋亡能力，并阐明其分子调控机理，期望发现基于肿瘤酸微环境的肝癌治疗新策略。

Metastasis is the major cause of poor prognosis and high fatality rate for hepatocellular carcinoma (HCC). Due to “Warburg effect”, an acidic tumor microenvironment widely exists in solid tumors and plays an important role in cancer metastasis. Thus, clarifying the mechanism of acidic tumor microenvironment in tumor metastasis could facilitate the development of the new therapeutic strategy for HCC. Our preliminary studies firstly found that acidic culture medium enhanced the anoikis resistant of HCC cells in vitro, which could be reversed by autophagy inhibitors. We proposed that acidic tumor microenvironment enhances anoikis resistant of HCC via inducing autophagy, finally promoting HCC metastasis. In this project, we will use HCC cell models, HCC xenograft mouse models and clinical HCC samples to identify and elucidate a new mechanism that acidic tumor microenvironment enhances anoikis resistant of HCC via inducing autophagy. Eventually, we could get some new ideas and targets based on tumor acidic microenvironment available for HCC treatment.