CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth

被引：1017

作者：

Ishimoto, Takatsugu ^{[1
,3
]}

Nagano, Osamu ^{[1
,2
]}

Yae, Toshifumi ^{[1
]}

Tamada, Mayumi ^{[1
]}

Motohara, Takeshi ^{[1
]}

Oshima, Hiroko ^{[4
]}

Oshima, Masanobu ^{[4
]}

Ikeda, Tatsuya ^{[5
]}

Asaba, Rika ^{[5
]}

Yagi, Hideki ^{[5
]}

Masuko, Takashi ^{[5
]}

Shimizu, Takatsune ^{[1
,2
]}

Ishikawa, Tomoki ^{[1
,6
]}

Kai, Kazuharu ^{[1
]}

Takahashi, Eri ^{[1
]}

Imamura, Yu ^{[3
]}

Baba, Yoshifumi ^{[3
]}

Ohmura, Mitsuyo ^{[7
]}

Suematsu, Makoto ^{[7
,8
]}

Baba, Hideo ^{[3
]}

Saya, Hideyuki ^{[1
,2
]}

机构：

[1] Keio Univ, Sch Med, Inst Adv Med Res, Div Gene Regulat,Shinjuku Ku, Tokyo 1608582, Japan

[2] Japan Sci & Technol Agcy, CREST, Tokyo 1608582, Japan

[3] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8608556, Japan

[4] Kanazawa Univ, Canc Res Inst, Div Genet, Kanazawa, Ishikawa 9200934, Japan

[5] Kinki Univ, Sch Pharm, Dept Pharmaceut Sci, Cell Biol Lab, Higashiosaka, Osaka 5778502, Japan

[6] Daiichi Sankyo Co Ltd, Kasai R&D Ctr, Edogawa Ku, Tokyo 1348630, Japan

[7] Keio Univ, Sch Med, Dept Biochem, Shinjuku Ku, Tokyo 1608582, Japan

[8] Japan Sci & Technol Agcy, ERATO Gas Biol Project, Tokyo 1608582, Japan

来源：

CANCER CELL | 2011年 / 19卷 / 03期

基金：

日本科学技术振兴机构;

关键词：

STEM-CELLS; PROSTAGLANDIN E-2; P38; MAPK; TRANSPORTER; ACTIVATION; WNT; DIFFERENTIATION; TUMORIGENESIS; MECHANISMS; EXPRESSION;

D O I：

10.1016/j.ccr.2011.01.038

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

CD44 is an adhesion molecule expressed in cancer stem-like cells. Here, we show that a CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and controls the intracellular level of reduced glutathione (GSH). Human gastrointestinal cancer cells with a high level of CD44 expression showed an enhanced capacity for GSH synthesis and defense against reactive oxygen species (ROS). Ablation of CD44 induced loss of xCT from the cell surface and suppressed tumor growth in a transgenic mouse model of gastric cancer. It also induced activation of p38(MAPK), a downstream target of ROS, and expression of the gene for the cell cycle inhibitor p21(CIP1/WAF1). These findings establish a function for CD44v in regulation of ROS defense and tumor growth.

引用

页码：387 / 400

页数：14

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