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蛋氨酸剥夺通过下调组织蛋白酶L抑制胶质瘤生长。

Methionine deprivation inhibits glioma growth through downregulation of CTSL.

作者信息

Qian Feng, Xu Haoyue, Zhang Yongkang, Li Linfeng, Yu Rutong

机构信息

Institute of Nervous System Diseases, Xuzhou Medical University Xuzhou 221002, Jiangsu, China.

Department of Neurosurgery, The First People's Hospital of Changzhou Changzhou 213003, Jiangsu, China.

出版信息

Am J Cancer Res. 2022 Nov 15;12(11):5004-5018. eCollection 2022.

Abstract

The metabolism of tumor cells is characterized by the regulation of demand, nutrient supply and metabolic enzymes, which are different in cancer tissues from those in corresponding healthy tissues. There is growing evidence that dietary composition influences biological processes that contribute to tumor incidence and progression as much as genetic status. One possibility for specific dietary interventions in cancer patients is to limit methionine intake. The role of methionine metabolism in tumors suggests that interference with the methionine metabolism network by either drug or environmental effects may show substantial therapeutic effects, but the molecular mechanism is not completely clear. In this study, methionine deprivation was found to downregulate cathepsin L (CTSL) and induce proliferation inhibition in glioma cells. We also demonstrated that CTSL is a tumor-related gene, and promotes the proliferation and invasion of glioma. Our results showed that the treatment of methionine metabolism and CTSL related genes in glioma cells may be a novel strategy for glioma therapy in the future.

摘要

肿瘤细胞的代谢特征在于对需求、营养供应和代谢酶的调节,这些在癌组织中与相应的健康组织不同。越来越多的证据表明,饮食组成对肿瘤发生和进展的生物学过程的影响与基因状态一样大。癌症患者进行特定饮食干预的一种可能性是限制甲硫氨酸的摄入。甲硫氨酸代谢在肿瘤中的作用表明,通过药物或环境效应干扰甲硫氨酸代谢网络可能显示出显著的治疗效果,但其分子机制尚不完全清楚。在本研究中,发现甲硫氨酸剥夺可下调组织蛋白酶L(CTSL)并诱导胶质瘤细胞增殖抑制。我们还证明CTSL是一个与肿瘤相关的基因,并促进胶质瘤的增殖和侵袭。我们的结果表明,治疗胶质瘤细胞中甲硫氨酸代谢和CTSL相关基因可能是未来胶质瘤治疗的一种新策略。

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