Functional analysis of key molecule of breast cancer stem cells

乳腺癌干细胞关键分子的功能分析

• 批准号: 23790357
• 负责人: HINOHARA Kunihiko
• 金额: $ 2.83万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790357/
• 关键词: breast cancer; cancer stem cells; HRG; ErbB; PI3K; IGF; IGF2; sphere; growth factor; ID3; がん幹細胞; 増殖因子; 乳がん; HER; NF-κB; breast cancer stem cells

We identified HRG/ErbB signaling as a key molecular mechanism on regulating breast cancer stem cell properties. ErbB signaling maintains breast cancer stem cell properties via PI3K/NF-kappaB pathway, suggesting that crosstalk between growth factor signaling and inflammatory response pathway is important for such regulation. Moreover, IGF2 signaling is required for maintenance of the breast cancer stem cell properties as a downstream mediator of PI3K signaling. Also, HRG signature and IGF signature identified by microarray analysis is strongly associated with both breast cancer grade and prognosis such as metastasis or relapse. These observations suggest that these growth factor signaling have important roles on malignant progression of breast cancer through maintenance of breast cancer stem cell properties.

我们确定HRG/ErbB信号转导是调节乳腺癌干细胞特性的关键分子机制。ErbB信号通过PI 3 K/NF-kappaB通路维持乳腺癌干细胞的特性，表明生长因子信号和炎症反应通路之间的串扰对于这种调节是重要的。此外，IGF 2信号传导是维持乳腺癌干细胞特性所必需的，作为PI 3 K信号传导的下游介质。此外，通过微阵列分析鉴定的HRG特征和IGF特征与乳腺癌分级和预后如转移或复发密切相关。这些观察结果表明，这些生长因子信号通过维持乳腺癌干细胞的特性，对乳腺癌的恶性进展具有重要作用。

项目成果

Effect of in vivo administration of reprogramming factors in the mouse liver.

• DOI: 10.3892/ol.2013.1418
• 发表时间: 2013-08
• 期刊: Oncology letters
• 影响因子: 2.9
• 作者: Tomokuni A;Eguchi H;Hoshino H;Dewi DL;Nishikawa S;Kano Y;Miyoshi N;Tojo A;Kobayashi S;Gotoh N;Hinohara K;Fusaki N;Saito T;Suemizu H;Wada H;Kobayashi S;Marubashi S;Tanemura M;Doki Y;Mori M;Ishii H;Nagano H
• 通讯作者: Nagano H

Epiregulin enhances tumorigenicity by activating the ERK/MAPK pathway in glioblastoma

• DOI: 10.1093/neuonc/not315
• 发表时间: 2014-07-01
• 期刊: NEURO-ONCOLOGY
• 影响因子: 15.9
• 作者: Kohsaka, Shinji;Hinohara, Kunihiko;Tanaka, Shinya
• 通讯作者: Tanaka, Shinya

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A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells.

一种 PI3K 依赖性基因表达程序，调节乳腺癌细胞的乳腺球形成。

• 发表时间: 2013
• 作者: Hinohara K;Shimamura T;Fukuda H;Tominaga K;Kanauchi H;Niida A;Tada K;Ogawa T;Miyano S;Gotoh N.
• 通讯作者: Gotoh N.

ErbB/NF-κB signaling controls self-renewal of breast cancer stem cells

ErbB/NF-κB信号传导控制乳腺癌干细胞的自我更新

• 发表时间: 2011
• 作者: Hinohara K;Kobayashi S;Umezawa K;Masaki Mori;Kanauchi H;Ogawa T;Inoue J;Tojo A;Gotoh N
• 通讯作者: Gotoh N