Author/Authors :
Ishimoto، نويسنده , , Takatsugu and Nagano، نويسنده , , Osamu and Yae، نويسنده , , Toshifumi and Tamada، نويسنده , , Mayumi and Motohara، نويسنده , , Takeshi and Oshima، نويسنده , , Hiroko and Oshima، نويسنده , , Masanobu and Ikeda، نويسنده , , Tatsuya and Asaba، نويسنده , , Rika and Yagi، نويسنده , , Hideki and Masuko، نويسنده , , Takashi and Shimizu، نويسنده , , Takatsune and Ishikawa، نويسنده , , Tomoki and Kai، نويسنده , , Kazuharu and Takahashi، نويسنده , , Eri and Imamura، نويسنده , , Yu and Baba، نويسنده , , Yoshifumi and Ohmura، نويسنده , , Mitsuyo and Suematsu، نويسنده , , Makoto and Baba، نويسنده , , Hideo and Saya، نويسنده , , Hideyuki، نويسنده ,
Abstract :
Summary
s 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 p38MAPK, a downstream target of ROS, and expression of the gene for the cell cycle inhibitor p21CIP1/WAF1. These findings establish a function for CD44v in regulation of ROS defense and tumor growth.
