ATF5通过调控TGFB2促进结直肠癌肝转移的分子机制及临床意义

肝转移是结直肠癌患者预后不良的重要因素，然而目前缺乏有效的预测靶标，且机制尚不明确。我们前期研究通过对病人原发灶和转移灶来源的样品进行配对的系统性分析，鉴定出肝转移特异性转录因子ATF5，进一步研究发现ATF5可能通过肿瘤转移相关基因TGFB2促进结直肠癌细胞的迁移及肿瘤转移的能力。我们推测：ATF5通过转录激活TGFB2促进结直肠癌的迁移，侵袭以及肿瘤转移。本项目拟基于临床样本进一步明确转录因子ATF5在结直肠癌肝转移中的调控作用及临床意义，同时结合体外以及体内实验动物研究阐明ATF5调控TGFB2以及肿瘤细胞迁移和肿瘤转移的分子机理，并以此为基础进一步探索ATF5作为结直肠癌肝转移预测靶标的潜在价值，同时初步探究靶向ATF5和TGFB2用于肿瘤治疗。本项目一方面将有助于进一步阐明结直肠癌肝转移的分子机理，另一方面可为结直肠癌肝转移的防治提供新的预测指标及潜在靶点和思路。

Liver metastasis is an important risk factor in the prognosis of colorectal cancer patients, yet there is a lack of effective predictive targets and the mechanism is unclear. Our previous study identified the liver metastasis-specific transcription factor ATF5 through second generation sequencing analysis of paired samples from patients' primary and metastatic tumors. We further investigated the ability of ATF5 to promote the migration of colorectal cancer cells and tumor metastasis possibly through the tumor metastasis-related gene TGFB2. This project aims to further clarify the regulatory role and clinical significance of ATF5 in colorectal cancer liver metastasis based on clinical samples, and to elucidate the molecular mechanism of ATF5 regulation of TGFB2 and tumor cell migration and metastasis based on in vitro and in vivo experiments. The project will also explore the value of ATF5 as a potential predictive marker for liver metastasis in colorectal cancer, and the use of targeting ATF5 and TGFB2 for cancer treatment. In conclusion, this project will help elucidating the molecular mechanism of liver metastasis in colorectal cancer, and provide new predictive indicators and potential targets for the prevention and treatment of colorectal cancer liver metastasis.