自噬与mTOR信号通路在维持舌癌干细胞干性特征中的相互调控作用及临床应用价值研究

The self-renew feature of tongue cancer stem cells is an important cause of the treatment failure of tongue cancer, thus, how to maintain characters of tongue cancer stem cells, such as self-renew feature, is a still hot-spot issues. Our previous studies found that the stemness characteristics of tongue cancer stem cells is accociated with the expressions of autophagic genes and the high levels of mTOR pathway rerative molecules in mammospheres and holoclone of tongue cancer. Based on aforementioned knowledge, the experiments will be planned in this project as following: In-depth investigate the regulation relationship between autophagic genes and mTOR signaling pathway; clear the regulation mechanism in tongue cancer stem cells have an important role in maintaining the stemness characteristics; and investigate and analyze the clinic value of this regulation for the early warning, early diagnosis and prognostic analysis of tongue cancer. The study will first elaborate the regulation mechanism of autophagy and mTOR signaling pathway and their role in the maintaining characteristics of tongue cancer stem cells. This might help us not only to elucidate the clinic significance of tongue cancer stem cells in the carcinogenesis of tongue cancer and the corresponding molecular mechanism, but to provide new experimental data for inhibitory treatment of tongue cancer stem cells.

癌干细胞的自我更新等干性特征是舌癌根治失败的重要原因，舌癌干细胞其干性特征如何维持仍是该研究领域的重要热点问题。本课题的前期研究发现在舌癌肿瘤球细胞中自噬基因和mTOR信号通路分子高水平表达，并与癌干细胞干性特征相关，以此为线索，开展如下研究：深入解析自噬与mTOR信号通路间的相互调控关系，明确这种调控机制在维持舌癌干细胞干性特性中的重要作用，并研究与分析它们在舌癌患者早期预警、早期诊断、和判断预后中的临床应用价值。以上研究将首次阐述自噬与mTOR信号通路间的调控机制以及该机制在维持舌癌干细胞特性中的作用，有助于进一步阐明舌癌干细胞在舌癌的发生和发展中的意义及分子机制，为舌癌干细胞抑制治疗的新策略提供实验依据。

研究背景：癌干细胞的自我更新等干性特征是舌癌根治失败的重要原因.在舌癌肿瘤球细胞中自噬基因和mTOR信号通路分子高水平表达，并与癌干细胞干性特征相关，但是自噬与mTOR信号通路间的相互调控关系，这种调控机制在维持舌癌干细胞干性特性中的作用机制尚未明晰。.主要研究内容：明确自噬和 mTOR 信号通路在维持舌癌干细胞干性特征中的作用及相关机制，并阐述其临床运用价值。.重要结果：明确自噬通过 mTOR 信号通路对舌癌干细胞的“干性”进行调控，明确自噬相关基因 FIP200、Atg7 沉默及联合抑制 mTOR 分子活性的负性效应可引起舌癌干细胞“干性”的极度抑制。.科学意义：本项目提示葛根素可能通过Beclin1抑制破骨细胞生长而发挥其治疗OP作用。