Title: Abstract 3719: xCT inhibition suppresses CD44v-positive stem-like tumor cells, which are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma.
Abstract: Abstract Given that cancer cells are exposed to environmental stressors such as oxygen or nutrient deficiency, low pH, inflammatory mediators, and ROS during tumor progression,the ability to avoid the consequences of such exposure is required for cancer cell survival. CD44 is a major marker for stem-like cancer cells in many epithelial tumors and has been implicated in tumor growth, invasion, and metastasis. CD44 exists in numerous variant isoforms (CD44v) that are generated through alternative mRNA splicing. We recently showed that interaction of CD44v with the cystine transporter subunit xCT stabilizes the latter protein and thereby potentiates the ability of cancer cells to defend themselves against reactive oxygen species (ROS). Stem-like cancer cells in which defense against ROS is enhanced by CD44v are thus thought to drive tumor growth, chemoresistance and metastasis. In the present study, we show that head and neck squamous cell carcinoma (HNSCC) cells that express CD44v rely on the activity of the cystine transporter subunit xCT for control of their redox status. Ablation of CD44v attenuated the xCT dependency as well as tumor-forming ability in HNSCC cells, and xCT inhibition selectively induced apoptosis in CD44v-expressing tumor cells. In contrast, CD44v-negative differentiated cells manifest epidermal growth factor receptor (EGFR) activation and rely largely on EGFR activity for their survival. Combined treatment with inhibitors of xCT-dependent cystine transport and of EGFR may induce apoptosis in distinct subpopulations of HNSCC tumor cells. Citation Format: Momoko Yoshitake, Osamu Nagano, Taneaki Nakagawa, Hideyuki Saya. xCT inhibition suppresses CD44v-positive stem-like tumor cells, which are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3719. doi:10.1158/1538-7445.AM2013-3719
Publication Year: 2013
Publication Date: 2013-04-01
Language: en
Type: article
Indexed In: ['crossref']
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