Activation of PI3 kinase/AKT pathway enhances degradation of EGFR

PI3 激酶/AKT 通路的激活增强 EGFR 的降解

• 批准号: 21790542
• 负责人: KURIBAYASHI Kageaki
• 金额: $ 2.83万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790542/
• 关键词: EGF受容体; PI3キナーゼ; EGF; 大腸癌; Akt

EGF receptor belongs to the receptor tyrosine kinases family that is activated by the cognate ligand including EGF, TGFα, and neuregulin. EGFR activate its downstream Ras, PI3 kinase and Akt pathway, which results in cell proliferation. Clinically, overexpression of EGFR predicts poor prognosis in many types of cancer. In this study, we analyzed the degradation mechanism of EGFR in order to enhance EGFR-targeted therapy. Akt activation and EGFR reduction took place after stimulating LS180 and SW480 colon cancer cell lines with EGF, confirmed by western blotting. LY294002, PI3 kinase inhibitor, inhibited Akt activation and subsequent EGFR degradation. Activation of PI3 kinase/Akt pathway by VEGF, or HGF did not affect the expression level of EGFR. Silencing of Akt by siRNA did not affect EGFR degradation. These results show EGFR degradation is regulated by PI3 kinase activity and tyrosine kinase activity of EGFR. Moreover, down regulation of EGFR was specific to EGF stimulation and not affected by insulin, VEGF, or HGF.

EGF受体属于受体酪氨酸激酶家族，该家族被包括EGF，TGFα和神经蛋白在内的同源配体激活。 EGFR激活其下游RAS，PI3激酶和AKT途径，从而导致细胞增殖。在临床上，EGFR的过表达预测了许多类型的癌症的预后不良。在这项研究中，我们分析了EGFR的降解机制，以增强EGFR靶向的治疗。 Akt激活和EGFR降低是在用EGF刺激LS180和SW480结肠癌细胞系后发生的，并通过Western blotting证实。 LY294002，PI3激酶抑制剂，抑制了AKT激活和随后的EGFR降解。 VEGF或HGF激活PI3激酶/AKT途径不会影响EGFR的表达水平。 siRNA对AKT的沉默不会影响EGFR降解。这些结果表明，EGFR降解受EGFR的PI3激酶活性和酪氨酸激酶活性调节。此外，调节EGFR是EGF刺激的特异性，不受胰岛素，VEGF或HGF的影响。

项目成果

SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer

• DOI: 10.3892/ijo.2011.929
• 发表时间: 2011-04-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Kobayashi, Daisuke;Kuribayshi, Kageaki;Watanabe, Naoki
• 通讯作者: Watanabe, Naoki

Sesamin induces autophagy in colon cancer cells by reducing tyrosine phosphorylation of EphA1 and EphB2

• DOI: 10.3892/ijo.2011.1011
• 发表时间: 2011-07-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Tanabe, Hiromi;Kuribayashi, Kageaki;Watanabe, Naoki
• 通讯作者: Watanabe, Naoki

腫瘍マーカーとしてのジアセチルスペルミンとジアセチルスペルミジンの評価

二乙酰精胺和二乙酰亚精胺作为肿瘤标志物的评价

• 发表时间: 2010
• 作者: 栗林景晶;大江由衣;梅森祥央;浅沼康一;佐藤和昭;田中真樹;小林大介;渡邉直樹
• 通讯作者: 渡邉直樹

肺癌におけるES細胞複製分子SALL4発現の意義

ES细胞复制分子SALL4在肺癌中表达的意义

• 发表时间: 2010
• 作者: 小林大介;ら
• 通讯作者: ら

High prevalence of human anti-mouse antibodies in the serum of colorectal cancer patients.

结直肠癌患者血清中人抗小鼠抗体的患病率很高。

• 发表时间: 2010
• 期刊: Anticancer Res
• 影响因子: 2
• 作者: 谷内一彦;長沼史登;中村正帆;吉川雄朗;Goto M
• 通讯作者: Goto M