XCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma

Momoko Yoshikawa, Kenji Tsuchihashi, Takatsugu Ishimoto, Toshifumi Yae, Takeshi Motohara, Eiji Sugihara, Nobuyuki Onishi, Takashi Masuko, Kunio Yoshizawa, Shuichi Kawashiri, Makio Mukai, Seiji Asoda, Hiromasa Kawana, Taneaki Nakagawa, Hideyuki Saya, Osamu Nagano

研究成果: Article査読

123 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1855-1866
ページ数12
ジャーナルCancer Research
73
6
DOI
出版ステータスPublished - 2013 3 15

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

フィンガープリント

「XCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル