Treatment of gastrointestinal cancer by targeting the distinct energy metabolism of cancer cells

针对癌细胞独特的能量代谢治疗胃肠癌

• 批准号: 23659643
• 负责人: MINAMOTO Toshinari
• 金额: $ 2.33万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659643/
• 关键词: 消化器がん; エネルギー代謝; 標的治療; GSK3β

Recently we discovered novel pathological roles for glycogen synthase kinase-3β (GSK3β) in promoting cancer cell survival and proliferation via the modulation of cell cycle, tumor suppressor and cell immortality pathways. This has led us to propose GSK3β as a potential target for cancer treatment. A primary role for GSK3β is the control of glycogen synthase activity that switches glycogenesis and glycolysis, the two major pathways of glucose metabolism. In this research, we investigated whether GSK3β influences the aberrant glucose metabolism in gastrointestinal cancer cells. Using innovative metabolomic technology, we found a distinctive metabolic trait in cancer cells that suggests inhibition of GSK3β attenuates glycolysis (Warburg effect) and restores mitochondrial glucose oxidation.This trait could be an important molecular basis for cancer treatment targeting aberrant GSK3β.

近年来，我们发现糖原合成酶激酶3β（glycogen synthase kinase-3β，GSK 3 β）通过调节细胞周期、肿瘤抑制因子和细胞永生化途径，在促进肿瘤细胞存活和增殖中发挥新的病理作用。这使我们提出GSK 3 β作为癌症治疗的潜在靶点。GSK 3 β的主要作用是控制糖原合酶活性，该活性转换糖原生成和糖酵解，这是葡萄糖代谢的两个主要途径。在本研究中，我们研究了GSK 3 β是否影响胃肠道癌细胞的糖代谢异常。利用创新的代谢组学技术，我们在癌细胞中发现了一个独特的代谢特征，即抑制GSK 3 β可以减弱糖酵解（瓦尔堡效应）并恢复线粒体葡萄糖氧化，这一特征可能是针对异常GSK 3 β的癌症治疗的重要分子基础。

项目成果

LINE-1 methylation level is a molecular marker with little intra-patient heterogeneity in primary and synchronous metastatic colorectal cancer.

LINE-1甲基化水平是原发性和同步转移性结直肠癌患者内异质性很小的分子标志物。

• 发表时间: 2012
• 作者: Matsunoki A;Kawakami K;Kotake M;KanekoM;Watanabe G;Minamoto T
• 通讯作者: Minamoto T

大腸がんにおけるmicrosatellite instabilityとCpG island methylator phenotypeの解析

结直肠癌微卫星不稳定性和CpG岛甲基化表型分析

• 发表时间: 2012
• 作者: Tanaka K;Morimoto Y;Toiyama Y;Matsushita K;Kawamura M;Koike Y;Okugawa Y;Inoue Y;Uchida K;Araki T;Mizoguchi A;Kusunoki M;宮下勝吉;小竹優範
• 通讯作者: 小竹優範

LINE-1メチル化は大腸がん細胞のオキザリプラチン・5-FU併用処理への感受性と相関する

LINE-1甲基化与结直肠癌细胞对奥沙利铂和5-FU联合治疗的敏感性相关

• 发表时间: 2012
• 作者: Kawamoto A;Yokoe T;Tanaka K;Saigusa S;Toiyama Y;Yasuda H;Inoue Y;Miki C;Kusunoki M;金子真美
• 通讯作者: 金子真美

Glycogen synthase kinase 3β inhibition sensitize human glioma cells to temozolomide by means of c-myc signaling

糖原合酶激酶 3β 抑制通过 c-myc 信号传导使人胶质瘤细胞对替莫唑胺敏感

• 发表时间: 2012
• 作者: 高原善博;吉富秀幸;高野重紹;賀川真吾;木村文夫;清水宏明;吉留博之;大塚将之;加藤厚;古川勝規;竹内男;高屋敷史;須田浩介;久保木知;賀川真吾;宮崎 勝;Pyko VI
• 通讯作者: Pyko VI

MAberrant glycogen synthase kinase 3β is involved in glioma invasion

MA异常糖原合酶激酶3β参与神经胶质瘤侵袭

• 发表时间: 2012
• 作者: Kawamoto A;Tanaka K;Saigusa S;Toiyama Y;Morimoto Y;Fujikawa H;Iwata T;Matsushita K;Yokoe T;Yasuda H;Inoue Y;Miki C;Kusunoki M;Mitsutoshi Nakada
• 通讯作者: Mitsutoshi Nakada