Nuclear receptors as molecular regulator and chemopreventive targets of colon cancer stem cells.

核受体作为结肠癌干细胞的分子调节剂和化学预防靶标。

• 批准号: 23501324
• 负责人: MASUDA Sonoko
• 金额: $ 3.24万
• 依托单位: Health Sciences University of Hokkaido
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-23501324/
• 关键词: 大腸がん幹細胞; 核内受容体; がん化学予防; 分子標的治療; ビタミンD; カロテノイド; 分子イメージング; がん遺伝子; 薬物代謝酵素; がん幹細胞標的分子; ビタミンＤ; フコキサンチノール; VDR; PPARG; RAR

Increasing evidence suggests that colon cancer stem cells (CCSC) have responsible for carcinogenesis, cancer development and recurrence. To establish signaling pathways in CCSC, which are implicated in the initiation and progression of colon cancer, we examined nuclear receptor signaling in colonospheres that are enriched in CCSC from established cell lines. We found that colonospheres formed by colon cancer cell lines are highly enriched in CCSC and that Wnt/b-catenin pathway plays a critical role in growth and maintenance of colonospheres. We also found that the combination of Fucoxanthinol and 1a,25-dihydroxyvitamin D3 acts on the CCSC cell growth through down-regulation of PPARg and NFkB p52, and as an intrinsic factor for the prevention of colon cancer. These findings establish a critical role for PPARg and vitamin D receptor (VDR) in growth regulation in colon cancer cells via functionally relevant cross-talk between these nuclear signaling pathways.

越来越多的证据表明，结肠癌干细胞（CCSC）与癌症的发生、发展和复发有关。为了在CCSC中建立与结肠癌发生和发展有关的信号通路，我们检测了来自已建立细胞系的CCSC中富集的结肠球中的核受体信号。我们发现结肠癌细胞系形成的结肠球高度富集CCSC，并且Wnt/b-catenin通路在结肠球的生长和维持中起关键作用。我们还发现岩藻黄嘌呤与1a，25-二羟基维生素D3联合通过下调PPARg和NFkB p52来作用于CCSC细胞的生长，并作为预防结肠癌的内在因素。这些发现证实了PPARg和维生素D受体（VDR）通过核信号通路之间的功能相关的串扰，在结肠癌细胞生长调控中起关键作用。

项目成果

Chemical-induced Carcinogenesis.

化学诱发的致癌作用。

• DOI: 10.1016/j.jecm.2013.10.009
• 发表时间: 2013
• 期刊: J. Exp. Clin. Med.
• 作者: Takuji Tanaka;Masahito Shimizu;Takahiro Kochi;and Hisataka Moriwaki
• 通讯作者: and Hisataka Moriwaki

Combined antiproliferative effect in dietary PPARγ regulating lipids against human colorectal cancer cells.

膳食 PPARγ 调节脂质对人结直肠癌细胞的联合抗增殖作用。

• 发表时间: 2011
• 作者: Masaru Terasaki;Hayato Maeda;Masahi Hosokawa;Kazuo Miyashita;Sonoko Masuda
• 通讯作者: Sonoko Masuda

ホウレン草由来 9’-cis-Neoxanthinによる大腸がん細胞増殖抑制作用機序

菠菜来源的9-顺式新黄质抑制结直肠癌细胞生长的作用机制

• 作者: 寺崎 将;太田友子;太田史子;近藤雄介;寺嶋 望;中島聖太;南 寿憲;安田友香;増田園子
• 通讯作者: 増田園子

Enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats.

• DOI: 10.3390/ijms140714700
• 发表时间: 2013-07-15
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Kochi T;Shimizu M;Ohno T;Baba A;Sumi T;Kubota M;Shirakami Y;Tsurumi H;Tanaka T;Moriwaki H
• 通讯作者: Moriwaki H

ニコチンはレチノイン酸代謝酵素CYP26A1の発現を低下させ乳癌の進行を抑制する

尼古丁通过降低视黄酸代谢酶 CYP26A1 的表达来抑制乳腺癌进展

• 发表时间: 2013
• 作者: 小山内誠;李康弘
• 通讯作者: 李康弘