Regulation and role of GLUT1 in hepatocellular carcinoma with focus on the interaction between tumor and activated hepatic stellate cells

GLUT1在肝细胞癌中的调控和作用，重点关注肿瘤与活化肝星状细胞之间的相互作用

• 批准号: 201482066
• 负责人: Professor Dr. Claus Hellerbrand
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/201482066?language=en
• 关键词: Regulation; role; GLUT1; hepatocellular; carcinoma

Cirrhosis is the main risk factor for hepatocellular carcinoma (HCC). Activated hepatic stellate cells (HSC) are the cellular source of the excessive matrix deposition and also infiltrate and form the HCC-stroma. We have shown that the expression of the glucose transporter GLUT1 is upregulated in HCC, and herewith, glycolysis, lactate secretion and tumorigenicity of HCC-cells is increased. Furthermore, we found that lactate induces the expression of protumorigenic factors in HSC. Moreover, we discovered that in addition to HCC cells also HSC express GLUT1. In this project we aim to further clarify the role of GLUT1 in hepatocancerogenesis and to analyze the role of GLUT1 in HSC for HCC development and progression. The ultimate aim of this project is to assess the potential of GLUT1 and factors, which affect GLUT1 and the metabolic HCC-HSC-interaction, respectively, as a novel prognostic markers and therapeutic targets in HCC.

肝硬化是肝细胞癌（HCC）的主要危险因素。活化的肝星状细胞（HSC）是过度基质沉积的细胞来源，也浸润并形成HCC-基质。我们已经表明，葡萄糖转运蛋白GLUT 1的表达在HCC中上调，因此，HCC细胞的糖酵解、乳酸分泌和致瘤性增加。此外，我们发现，乳酸诱导表达的促肿瘤因子在HSC。此外，我们发现除了HCC细胞外，HSC也表达GLUT 1。在本项目中，我们的目标是进一步阐明GLUT 1在肝癌发生中的作用，并分析GLUT 1在HSC中对肝癌发生和进展的作用。本项目的最终目的是评估GLUT 1和影响GLUT 1和代谢HCC-HSC相互作用的因素，分别作为HCC的新的预后标志物和治疗靶点的潜力。

项目成果

Cylindromatosis Gene CYLD Regulates Hepatocyte Growth Factor Expression in Hepatic Stellate Cells Through Interaction With Histone Deacetylase 7

• DOI: 10.1002/hep.27209
• 发表时间: 2014-09-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Pannem, Rajeswara R.;Dorn, Christoph;Massoumi, Ramin
• 通讯作者: Massoumi, Ramin

Effect of melanoma cells on proliferation and migration of activated hepatic stellate cells in vitro.

黑色素瘤细胞对体外活化肝星状细胞增殖和迁移的影响

• DOI: 10.1016/j.prp.2016.12.014
• 发表时间: 2017
• 期刊: Pathology, research and practice
• 作者: Meyer T;Koch A;Ebert EV;Czech B;Mueller M;Bosserhoff A;Lang SA;Hellerbrand C
• 通讯作者: Hellerbrand C

ERK activation and autophagy impairment are central mediators of irinotecan-induced steatohepatitis

• DOI: 10.1136/gutjnl-2016-312485
• 发表时间: 2018-04-01
• 期刊: GUT
• 影响因子: 24.5
• 作者: Mahli, Abdo;Saugspier, Michael;Hellerbrand, Claus
• 通讯作者: Hellerbrand, Claus

Analysis of a promoter polymorphism of the GLUT1 gene in patients with hepatocellular carcinoma

• DOI: 10.3109/09687688.2011.554447
• 发表时间: 2011-04-01
• 期刊: MOLECULAR MEMBRANE BIOLOGY
• 作者: Amann, Thomas;Kirovski, Georgi;Hellerbrand, Claus
• 通讯作者: Hellerbrand, Claus

Wild type Kirsten rat sarcoma is a novel microRNA-622-regulated therapeutic target for hepatocellular carcinoma and contributes to sorafenib resistance

• DOI: 10.1136/gutjnl-2017-315402
• 发表时间: 2018-07-01
• 期刊: GUT
• 影响因子: 24.5
• 作者: Dietrich, Peter;Koch, Andreas;Hellerbrand, Claus
• 通讯作者: Hellerbrand, Claus