Functional analysis of Smoothened in osteosarcoma via signal cross talk

通过信号串扰对骨肉瘤中的 Smoothened 进行功能分析

• 批准号: 22591663
• 负责人: YAMAMOTO Takuya
• 金额: $ 3万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591663/
• 关键词: 骨肉腫; Hedgehog Smoothened; 転移; Hedgehog; GLI2; 細胞増殖; 細胞浸潤; 細胞周期

We have examined the function of Hedgehog pathway in osteosarcoma cell proliferation, metastasis, and cancer stem cells. We found activation of Hedgehog pathway in human osteosarcoma. Inhibition of Smoothened (SMO) prevented osteosarcoma cell proliferation by cell cycle regulation in vitro and in vivo. In addition, pharmacological inhibition of SMO or GLI prevents human rhabdomyosarcoma cell proliferation. Furthermore, inhibition of GLI2 prevents osteosarcoma cell proliferation, invasion, and lung metastasis. We have already found that other signal related molecule regulate the osteosarcoma cell metastasis by Hedgehog signal activation.

我们研究了Hedgehog通路在骨肉瘤细胞增殖、转移和肿瘤干细胞中的作用。我们在人骨肉瘤中发现了Hedgehog通路的激活。抑制Smoothened(SMO)通过调节细胞周期抑制骨肉瘤细胞的增殖。此外，SMO或GLI的药理抑制可阻止人横纹肌肉瘤细胞的增殖。此外，抑制GLI2可以阻止骨肉瘤细胞的增殖、侵袭和肺转移。我们已经发现其他信号相关分子通过Hedgehog信号激活来调节骨肉瘤细胞的转移。

项目成果

Suppression of osteosarcoma cell invasion by chemotherapy is mediated by urokinase plasminogen activator activity via up-regulation of EGR1.

化疗对骨肉瘤细胞侵袭的抑制是由尿激酶纤溶酶原激活剂活性通过上调 EGR1 介导的。

• DOI: 10.1371/journal.pone.0016234
• 发表时间: 2011-01-20
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Matsunoshita Y;Ijiri K;Ishidou Y;Nagano S;Yamamoto T;Nagao H;Komiya S;Setoguchi T
• 通讯作者: Setoguchi T

Role of GLI2 in the growth of human osteosarcoma

• DOI: 10.1002/path.2880
• 发表时间: 2011-06-01
• 期刊: JOURNAL OF PATHOLOGY
• 影响因子: 7.3
• 作者: Nagao, Hiroko;Ijiri, Kosei;Setoguchi, Takao
• 通讯作者: Setoguchi, Takao

Upregulation of Notch pathway molecules in oral squamous cell carcinoma

• DOI: 10.3892/ijo_00000558
• 发表时间: 2010-04-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Hijioka, Hiroshi;Setoguchi, Takao;Nakamura, Norifumi
• 通讯作者: Nakamura, Norifumi

Kawabata N, Ijiri K, Ishidou Y, Yamamoto T, Nagao H, Nagano S, Maeda S, Komiya S, Setoguchi T†.

Kawabata N、Ijiri K、Ishidou Y、Yamamoto T、Nagao H、Nagano S、Maeda S、Komiya S、Setoguchi T†。

• 发表时间: 2011
• 期刊: Corresponding author Int J Oncol
• 作者: 柿本拓也;西村明展;福田亜紀;加藤公;須藤啓広;A Matsumine;松峯昭彦;Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth
• 通讯作者: Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

骨軟部肉腫に対する新規分子標的治療

骨和软组织肉瘤的新型分子靶向治疗

• 发表时间: 2012
• 作者: 瀬戸口啓夫;小宮節郎
• 通讯作者: 小宮節郎