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

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• 作者：Takatsugu Ishimoto¹ ; ³ ; Osamu Nagano¹ ; ² ; ^{osmna@sb3.so-net.ne.jp} ; Toshifumi Yae¹ ; Mayumi Tamada¹ ; Takeshi Motohara¹ ; Hiroko Oshima⁴ ; Masanobu Oshima⁴ ; Tatsuya Ikeda⁵ ; Rika Asaba⁵ ; Hideki Yagi⁵ ; Takashi Masuko⁵ ; Takatsune Shimizu¹ ; ² ; Tomoki Ishikawa¹ ; ⁶ ; Kazuharu Kai¹ ; Eri Takahashi¹ ; Yu Imamura³ ; Yoshifumi Baba³ ; Mitsuyo Ohmura⁷ ; Makoto Suematsu⁷ ; ⁸ ; Hideo Baba³ ; Hideyuki Saya¹ ; ²
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：8 March 2011
• 年：2011
• 卷：19
• 期：3
• 页码：387-400
• 全文大小：2505 K

文摘

Summary

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.