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

Takatsugu Ishimoto, Osamu Nagano, Toshifumi Yae, Mayumi Tamada, Takeshi Motohara, Hiroko Oshima, Masanobu Oshima, Tatsuya Ikeda, Rika Asaba, Hideki Yagi, Takashi Masuko, Takatsune Shimizu, Tomoki Ishikawa, Kazuharu Kai, Eri Takahashi, Yu Imamura, Yoshifumi Baba, Mitsuyo Ohmura, Makoto Suematsu, Hideo BabaHideyuki Saya

研究成果: Article

534 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)387-400
ページ数14
ジャーナルCancer Cell
19
発行部数3
DOI
出版物ステータスPublished - 2011 3 8

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Oxidation-Reduction
Reactive Oxygen Species
Growth
Amino Acid Transport System X-AG
cdc Genes
Neoplasms
Gastrointestinal Neoplasms
Cystine
Neoplastic Stem Cells
p38 Mitogen-Activated Protein Kinases
Transgenic Mice
Stomach Neoplasms
Glutathione

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

これを引用

CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth. / Ishimoto, Takatsugu; Nagano, Osamu; Yae, Toshifumi; Tamada, Mayumi; Motohara, Takeshi; Oshima, Hiroko; Oshima, Masanobu; Ikeda, Tatsuya; Asaba, Rika; Yagi, Hideki; Masuko, Takashi; Shimizu, Takatsune; Ishikawa, Tomoki; Kai, Kazuharu; Takahashi, Eri; Imamura, Yu; Baba, Yoshifumi; Ohmura, Mitsuyo; Suematsu, Makoto; Baba, Hideo; Saya, Hideyuki.

:: Cancer Cell, 巻 19, 番号 3, 08.03.2011, p. 387-400.

研究成果: Article

Ishimoto, T, Nagano, O, Yae, T, Tamada, M, Motohara, T, Oshima, H, Oshima, M, Ikeda, T, Asaba, R, Yagi, H, Masuko, T, Shimizu, T, Ishikawa, T, Kai, K, Takahashi, E, Imamura, Y, Baba, Y, Ohmura, M, Suematsu, M, Baba, H & Saya, H 2011, 'CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth', Cancer Cell, 巻. 19, 番号 3, pp. 387-400. https://doi.org/10.1016/j.ccr.2011.01.038
Ishimoto, Takatsugu ; Nagano, Osamu ; Yae, Toshifumi ; Tamada, Mayumi ; Motohara, Takeshi ; Oshima, Hiroko ; Oshima, Masanobu ; Ikeda, Tatsuya ; Asaba, Rika ; Yagi, Hideki ; Masuko, Takashi ; Shimizu, Takatsune ; Ishikawa, Tomoki ; Kai, Kazuharu ; Takahashi, Eri ; Imamura, Yu ; Baba, Yoshifumi ; Ohmura, Mitsuyo ; Suematsu, Makoto ; Baba, Hideo ; Saya, Hideyuki. / CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth. :: Cancer Cell. 2011 ; 巻 19, 番号 3. pp. 387-400.
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AU - Tamada, Mayumi

AU - Motohara, Takeshi

AU - Oshima, Hiroko

AU - Oshima, Masanobu

AU - Ikeda, Tatsuya

AU - Asaba, Rika

AU - Yagi, Hideki

AU - Masuko, Takashi

AU - Shimizu, Takatsune

AU - Ishikawa, Tomoki

AU - Kai, Kazuharu

AU - Takahashi, Eri

AU - Imamura, Yu

AU - Baba, Yoshifumi

AU - Ohmura, Mitsuyo

AU - Suematsu, Makoto

AU - Baba, Hideo

AU - Saya, Hideyuki

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