肿瘤干细胞有抗放化疗特性，是肿瘤复发转移的重要因素之一。mTORC1是调控肿瘤代谢的重要复合物，但其在肿瘤干细胞中的功能尚不明确。前期成果中我们发现胶质瘤干细胞mTORC1活性低并能抑制肿瘤干细胞的分化，抵抗一线化疗药替莫唑胺。预实验中我们发现mTORC1上游氨基酸转运体CD98/LAT1在胶质瘤干细胞中表达量与分化肿瘤细胞相同，但胶质瘤干细胞对氨基酸刺下mTORC1激活的反应较分化肿瘤细胞慢且弱，CD98/LAT1能从细胞膜定位到溶酶体膜上，因此我们猜测CD98/LAT1的定位转移可能是维持胶质瘤干细胞mTORC1低活性的关键。故本项目拟采用细胞分子生物学和临床病理学方法，明确CD98/LAT1定位变化在调控肿瘤干细胞mTORC1活性中的机制；进一步探索mTORC1低活性与抗化疗和临床预后的关系。从而揭示CD98/LAT1负调控胶质瘤干细胞mTORC1与干性维持和抵抗化疗的内在关系。

Glioma stem cell has anti-chemo-radiation characteristic, which is an important factor involved in tumor metastasis and recurrence. mTORC1 is a key complex in tumor cell metabolism, while its function in tumor stem cell remains controversial. In our previous report, we found low mTORC1 activities in glioma stem cells compare to their induced differentiated mature tumor cells. The low mTORC1 activities suppress the tumor stem cell induced differentiation. And glioma stem cells were not sensitive to timozolomide. Our preliminary data revealed identical expression levels of amino acid transporter CD98/LAT1, the upper stream of mTORC1, in glioma stem cells and differentiated cells. However, amino acid stimulation test showed slower and weaker activation of mTORC1. And CD98/LAT1 could be localized onto lysosome membrane from cell membrane. Thus, we hypothesize that the localization of CD98/LAT1 to lysosome membrane might be a key process in maintaining low mTORC1 activity in glioma stem cell. In this project, we aim to verify the mechanism of CD98/LAT1 re-localization in regulating mTORC1 activities in glioma stem cell, and explore the function of low mTORC1 in anti-chemotherapy abilities of tumor stem cells and its relation to clinical outcomes. In this project, we would like to clarify the negative regulation of mTORC1 by CD98/LAT1 in glioma stem cell and its relation with anti-chemotherapy ability.