Identification of new therapeutic target molecules for renal cell carcinoma

肾细胞癌新治疗靶分子的鉴定

• 批准号: 24659712
• 负责人: NAKAMURA Eijiro
• 金额: $ 2.25万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659712/
• 关键词: 腎細胞癌; VHL; Renal Cell Carcinoma

Recently, the number of RCC patients is increasing. Although, anti-VEGF therapies improve the prognosis of those patients, most of tumors acquire resistance and finally progress. It has been reported that VHL gene is mutated in 70% of RCC and we showed that clusterin was regulated by pVHL. It was suggested clusterin had a tumor suppressor function since this molecule is down regulated by pVHL. Based on these, we have cloned the promoter region of clusterin to examine the regulation mechanisms of the protein as well as the identification of new therapeutic target for RCC. As a result of this, MAP2K1 was identified as new molecular therapeutic target for RCC.

近年来，肾细胞癌患者数量呈上升趋势。尽管抗血管内皮生长因子治疗改善了这些患者的预后，但大多数肿瘤获得耐药性并最终进展。已有研究表明，VHL基因在70%的肾细胞癌中发生突变，且聚集素受pVHL调控。有人认为，聚集素具有肿瘤抑制功能，因为该分子被pVHL下调。在此基础上，我们克隆了聚集素的启动子区域，以研究该蛋白的调控机制以及寻找新的肾癌治疗靶点。因此，MAP2K1被确定为肾癌新的分子治疗靶点。

项目成果

The transcription factor Sp3 regulates the expression of a metastasis-related marker of sarcoma, actin filament-associated protein 1-like 1 (AFAP1L1).

• DOI: 10.1371/journal.pone.0049709
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kajita Y;Kato T Jr;Tamaki S;Furu M;Takahashi R;Nagayama S;Aoyama T;Nishiyama H;Nakamura E;Katagiri T;Nakamura Y;Ogawa O;Toguchida J
• 通讯作者: Toguchida J

Tumor microvasculature with endothelial fenestrations in VHL null clear cell renal cell carcinomas as a potent target of anti-angiogenic therapy

VHL 无效透明细胞肾细胞癌中具有内皮开窗的肿瘤微血管作为抗血管生成治疗的有效靶点

• 发表时间: 2012
• 期刊: Cancer Sci
• 影响因子: 5.7
• 作者: Yamasaki T;Nishiyama H.
• 通讯作者: Nishiyama H.

SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer.

• DOI: 10.1016/j.ccr.2013.10.025
• 发表时间: 2013-12-09
• 期刊: Cancer cell
• 影响因子: 50.3
• 作者: Li L;Shen C;Nakamura E;Ando K;Signoretti S;Beroukhim R;Cowley GS;Lizotte P;Liberzon E;Bair S;Root DE;Tamayo P;Tsherniak A;Cheng SC;Tabak B;Jacobsen A;Hakimi AA;Schultz N;Ciriello G;Sander C;Hsieh JJ;Kaelin WG Jr
• 通讯作者: Kaelin WG Jr

JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma

• DOI: 10.1038/onc.2011.475
• 发表时间: 2012-06-01
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Kanno, T.;Kamba, T.;Nakamura, E.
• 通讯作者: Nakamura, E.

Downregulation of Ral GTPase-activating protein promotes tumor invasion and metastasis of bladder cancer

• DOI: 10.1038/onc.2012.101
• 发表时间: 2013-02-14
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Saito, R.;Shirakawa, R.;Horiuchi, H.
• 通讯作者: Horiuchi, H.