Lipid metabolomics to analyze the mechanisms for cellular adaptation to tumor microenvironment

脂质代谢组学分析细胞适应肿瘤微环境的机制

• 批准号: 22650230
• 负责人: SEIMIYA Hiroyuki
• 金额: $ 2.12万
• 依托单位: 公益財団法人がん研究会 (2011)Japanese Foundation For Cancer Research (2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22650230/
• 关键词: 脂質代謝; 細胞増殖; がん; 微小環境; メタボローム; ATP-クエン酸リアーゼ; 活性酸素; 酸化ストレス; 脂質; バイオマーカー; 細胞死

Cancer cells often enhance de novo lipid synthesis. However, its functional significance remains unknown. In this study, we found that depletion of a lipid-synthesizing enzyme, called ATP citrate lyase(ACLY), blocks cancer cell growth. This anticancer effect was more evident in those cells with lower reactive oxygen species(ROS) and lower phosphorylation level of AMPK. ACLY depletion elevated the relative abundance of palmitate. Because palmitate can induce ROS, it may contribute to the anticancer effect of ACLY depletion. In clinical colon tumors, higher malignant grades correlated with lower levels of AMPK phosphorylation and oxidative stress, suggesting that ACLY inhibition can be utilized as an anticancer therapeutics.

癌细胞通常会增强脂质的从头合成。然而，其功能意义仍然未知。在这项研究中，我们发现一种叫做ATP柠檬酸裂解酶（ACLY）的脂质合成酶的耗尽会阻止癌细胞的生长。这种抗癌作用在活性氧（ROS）和AMPK磷酸化水平较低的细胞中更为明显。ACLY消耗升高棕榈酸的相对丰度。由于棕榈酸可以诱导ROS，它可能有助于ACLY消耗的抗癌作用。在临床结肠肿瘤中，较高的恶性等级与较低水平的AMPK磷酸化和氧化应激相关，表明ACLY抑制可用作抗癌治疗剂。

项目成果

Pharmacological Targeting of Constitutively Active Truncated Androgen Receptor by Nigericin and Suppression of Hormone-Refractory Prostate Cancer Cell Growth

• DOI: 10.1124/mol.110.064790
• 发表时间: 2010-11-01
• 期刊: MOLECULAR PHARMACOLOGY
• 影响因子: 3.6
• 作者: Mashima, Tetsuo;Okabe, Sachiko;Seimiya, Hiroyuki
• 通讯作者: Seimiya, Hiroyuki

脂質代謝酵素を標的とした乳癌、前立腺癌の治療とその分子機構

脂质代谢酶靶向治疗乳腺癌和前列腺癌及其分子机制

• 发表时间: 2011
• 作者: 右田敏郎;岡部幸子;清宮啓之
• 通讯作者: 清宮啓之

Involvement of constitutively active truncated androgen receptor(tAR) in hormone-refractory prostate cancer growth and the tAR inhibition by nigericin

组成型活性截短型雄激素受体（tAR）参与激素难治性前列腺癌生长以及尼日利亚霉素对 tAR 的抑制

• 发表时间: 2011
• 作者: Mashima T.;Okabe S.;Seimiya H.
• 通讯作者: Seimiya H.

A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor

一种新型的基于酵母细胞的筛选将黄酮鉴定为坦科聚合酶抑制剂

• 发表时间: 2010
• 期刊: Biochem Biophys Res Commun 394
• 作者: 遠藤玉樹;宍戸昌彦;大槻高史;Yashiroda Y
• 通讯作者: Yashiroda Y

Generation of Induced Pluripotent Stem Cells from Human Terminally Differentiated Circulating T Cells

• DOI: 10.1016/j.stem.2010.06.003
• 发表时间: 2010-07-02
• 期刊: CELL STEM CELL
• 影响因子: 23.9
• 作者: Seki, Tomohisa;Yuasa, Shinsuke;Fukuda, Keiichi
• 通讯作者: Fukuda, Keiichi