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Publication : CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth.

First Author  Ishimoto T Year  2011
Journal  Cancer Cell Volume  19
Issue  3 Pages  387-400
PubMed ID  21397861 Mgi Jnum  J:169929
Mgi Id  MGI:4943605 Doi  10.1016/j.ccr.2011.01.038
Citation  Ishimoto T, et al. (2011) CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc(-) and Thereby Promotes Tumor Growth. Cancer Cell 19(3):387-400
abstractText  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.
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