自噬是细胞内主要降解系统，参与细胞能量和物质代谢的动态平衡，与细胞生存和凋亡事件相关，诱导肿瘤细胞自噬成为肿瘤治疗的重要研究方向。本课题组前期发现雷公藤甲素（Tp）刺激、低糖培养可诱导结直肠癌（CRC）细胞自噬，并伴随着转运蛋白14-3-3ε移位出核和hnRNP C1/C2蛋白水平下降。hnRNP C1/C2有调控肿瘤细胞增殖和侵袭作用，表达下调后抑制负调控自噬的关键蛋白mTOR；生物信息学分析表明hnRNP C1/C2为14-3-3ε结合蛋白。据此，本研究提出如下假说：在Tp、低糖等自噬诱导剂作用下，CRC细胞中14-3-3ε与hnRNP C1/C2相互作用，并转运其出核进入胞质；hnRNP C1/C2在胞质中通过自噬溶酶体或蛋白酶体途径降解，自噬负调控分子mTOR下调，使CRC细胞自噬作用增强。本研究有助于进一步了解药物或细胞微环境对癌细胞自噬的促进机制，为CRC治疗提供新的理论依据。

Autophagy is a basic cellular catabolic process that is involved in maintaining the homeostasis of cellular engery and metabolism. Due to the high association with cell survival and apoptosis, it has become a hot spot in the study of cancer theraputics. In our previous study, we found that triptolide (Tp) or low glucose media culture could induce the autophagy in colorectal cancer (CRC) cells, which companied by the translocation of 14-3-3ε from nuclear into cytoplasm and the downregulation of hnRNP C1/C2 protein. It has suggested that hnRNP C1/C2 protein could regulate the proliferation and invasion of cancer cells. Downregulation of hnRNP C1/C2 was reported to inhibit mTOR, which could negtively regulate autophagy. Further bioinformatic analysis and literature review implicate that hnRNP C1/C2 protein can directly interact with 14-3-3ε, suggesting that 14-3-3ε enables the translocation of hnRNP C1/C2 and eventually causes its degradation outside the nuclear. The objective of this project is to investigate detailed machnisms of Tp-induced autophagy based on the interaction between 14-3-3ε and hnRNP C1/C2. We hypothesize that autophagy inducers such as Tp and low glucose can enhance the 14-3-3ε interation with hnRNP C1/C2 in CRC cells and further increase the translocation of these two proteins, finally resulting in hnRNP C1/C2 breakdown in cytoplasm. Due to hnRNP C1/C2 breakdown, mTOR is consequently suppressed. The downregulated mTOR will promote the progress of autophagy. This study will help us disclose some novel machanisms of autophagy and further understand the autophagy of cancer cells initiated by drugs or cell microenvironment.