Regulation of metabolic shift by drs tumor suppressor gene

drs抑癌基因对代谢转变的调控

• 批准号: 23590457
• 负责人: TAMBE Yukihiro
• 金额: $ 3.41万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590457/
• 关键词: 癌; 代謝; 癌抑制遺伝子; メタボローム; グルコース代謝; drs; 乳酸脱水素酵素; エネルギー代謝; ワールブルグ効果

The drs gene is the tumor suppressor gene that regulates apoptosis and autophagy in cancer cells. However, its physiologic function in normal cells is unclear. In this study, by using drs knockout (KO) mouse embryonic fibroblast cells, we found that genetic loss of drs induces the metabolic shift toward aerobic glycolysis by increasing the expression and activity of lactose dehydrogenase (LDH). It is suggested that drs participates in the regulation of glucose metabolism and down-regulation of drs during tumorigenesis is involved in the induction of Warburg effect in human cancers. We also found that the induction of drs into KO cells and the treatment of cancer cells with LDH inhibitor could suppress the metabolic shift and the malignant transformation. Further investigations will contribute toward developing a new anticancer therapy.

drs基因是调节癌细胞凋亡和自噬的肿瘤抑制基因。然而，其在正常细胞中的生理功能尚不清楚。在这项研究中，通过使用drs敲除（KO）小鼠胚胎成纤维细胞，我们发现，drs的遗传丢失诱导代谢转向有氧糖酵解通过增加乳糖脱氢酶（LDH）的表达和活性。提示drs参与糖代谢的调节，肿瘤发生过程中drs的下调参与了肿瘤瓦尔堡效应的诱导。我们还发现，诱导drs进入KO细胞和用LDH抑制剂处理癌细胞可以抑制代谢转移和恶性转化。进一步的研究将有助于开发新的抗癌疗法。

项目成果

Molecular mechanism of female-specific rectal carcinogenesis in cyclin D1b transgenic mice

cyclin D1b转基因小鼠雌性特异性直肠癌发生的分子机制

• 作者: Chul Jang Kim;Yukihiro Tambe;Ken-ichi Mukaisho;Hiroyuki Sugihara;Hirokazu Inoue
• 通讯作者: Hirokazu Inoue

Female-specific development of rectal cancers via serrated pathway in cyclin D1b-transgenic mice

细胞周期蛋白 D1b 转基因小鼠中通过锯齿状途径发生直肠癌的雌性特异性

• 发表时间: 2012
• 作者: Yukihiro Tambe;Chul Jang Kim;Ken-ichi Mukaisho;Hiroyuki Sugihara;Takahiro Isono;Hiromichi Sonoda;Tomoharu Shimizu;Gen Kondoh;Hirokazu Inoue
• 通讯作者: Hirokazu Inoue

Role of cyclin D1b variant in rectal tumorigenesis

细胞周期蛋白 D1b 变异在直肠肿瘤发生中的作用

• 发表时间: 2011
• 作者: Chul Jang Kim;Yukihiro Tambe;Takahiro Isono;Ken ichi Mukaisho;Hiroyuki Sugihara;Gen Kondoh;Hirokazu Inoue
• 通讯作者: Hirokazu Inoue

Suppression of viral replication by drs tumor suppressor via mTOR dependent pathway

drs肿瘤抑制因子通过mTOR依赖性途径抑制病毒复制

• DOI: 10.1016/j.canlet.2011.09.015
• 发表时间: 2012
• 期刊: Cancer Letters
• 影响因子: 9.7
• 作者: Tambe;Y.;et al
• 通讯作者: et al

The drs tumor suppressor gene is involved in regulation of Warburg effect

drs抑癌基因参与Warburg效应的调节

• 发表时间: 2012
• 作者: Yukihiro Tambe;Hirokazu Inoue
• 通讯作者: Hirokazu Inoue