KLF2蛋白通过反馈抑制TGF-β信号减弱肝癌细胞EMT和运动能力的分子机理

肝细胞癌（hepatocellular carcinoma，HCC）是最主要的原发性肝癌，是我国癌症相关死亡的主要原因之一；上皮细胞-间质细胞转变（EMT）对促进HCC细胞运动和恶性发展具有重要意义。TGF-β是体内诱导EMT和促进HCC细胞运动的主要细胞因子之一；时空特异性信号调控与TGF-β发挥的生物学功能密切相关。KLF2是KLF转录因子家族的成员之一；前期我们发现KLF2能在HCC细胞中通过反馈机制抑制TGF-β/Smad信号，并减弱TGF-β诱导的EMT相关基因表达和癌细胞运动能力，如癌细胞迁移与侵袭。本项目致力于阐明KLF2反馈调控TGF-β信号的分子机制，及其通过TGF-β信号减弱肝癌细胞EMT和运动的作用和机理。预期成果有助于进一步认识KLF2的分子作用和TGF-β信号调控机制，及其在肝癌细胞EMT和运动中的功能，并为肝癌靶向干预提供新的靶点和策略。

Hepatocellular carcinoma (HCC) is the main form of primary liver cancers, and is one of the main causes of cancer-related death in China. Epithelial-mesenchymal transition (EMT) plays an important role in promoting cancer cell motility and malignant development in HCC. TGF-β is one of the major inducers of EMT and HCC cell motility in vivo, and the spatio-temporal specific signaling regulation is crucial for TGF-β to exert its functions in this regard. KLF2 is a member of the KLF transcription factor protein family. Our unpublished data indicate that KLF2 could inhibit TGF-β/Smad signaling through a feedback circuit in HCC, attenuating TGF-β-induced expression of EMT-related genes and cancer cell motility, such as migration and invasion. This proposal aims to elucidate the molecular mechanisms underlying KLF2-mediated feedback regulation of TGF-β signaling and their roles in HCC cell EMT and motility. The expected results would further our understanding as to how TGF-β signaling is regulated by KLF2, and how this regulation makes sense in liver cancer cell EMT and motility. Furthermore, the study may also provoke new strategies or provide new molecular targets for targeted intervention in liver cancer.