論文 - 詳細
| RRC ID | 44240 |
|---|---|
| 著者 | Yoshikawa M, Tsuchihashi K, Ishimoto T, Yae T, Motohara T, Sugihara E, Onishi N, Masuko T, Yoshizawa K, Kawashiri S, Mukai M, Asoda S, Kawana H, Nakagawa T, Saya H, Nagano O. |
| タイトル | xCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. |
| ジャーナル | Cancer Res |
| Abstract |
The targeting of antioxidant systems that allow stem-like cancer cells to avoid the adverse consequences of oxidative stress might be expected to improve the efficacy of cancer treatment. Here, we show that head and neck squamous cell carcinoma (HNSCC) cells that express variant isoforms of CD44 (CD44v) rely on the activity of the cystine transporter subunit xCT for control of their redox status. xCT inhibition selectively induces apoptosis in CD44v-expressing tumor cells without affecting CD44v-negative differentiated cells in the same tumor. In contrast to CD44v-expressing undifferentiated cells, CD44v-negative differentiated cells manifest EGF receptor (EGFR) activation and rely on EGFR activity for their survival. Combined treatment with inhibitors of xCT-dependent cystine transport and of EGFR resulted in a synergistic reduction of EGFR-expressing HNSCC tumor growth. Thus, xCT-targeted therapy may deplete CD44v-expressing undifferentiated HNSCC cells and concurrently sensitize the remaining differentiating cells to available treatments including EGFR-targeted therapy. |
| 巻・号 | 73(6) |
| ページ | 1855-66 |
| 公開日 | 2013-3-15 |
| DOI | 10.1158/0008-5472.CAN-12-3609-T |
| PII | 0008-5472.CAN-12-3609-T |
| PMID | 23319806 |
| MeSH | Amino Acid Transport System y+ / antagonists & inhibitors* Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / immunology* Carcinoma, Squamous Cell / pathology Cell Differentiation ErbB Receptors / drug effects* Head and Neck Neoplasms / drug therapy Head and Neck Neoplasms / immunology* Head and Neck Neoplasms / pathology Humans Hyaluronan Receptors / immunology* |
| IF | 9.727 |
| 引用数 | 106 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) |