NKX2-1/TITF1/TTF-1-Induced ROR1 Is Required to Sustain EGFR Survival Signaling in Lung Adenocarcinoma

Tomoya Yamaguchi, Kiyoshi Yanagisawa, Ryoji Sugiyama, Yasuyuki Hosono, Yukako Shimada, Chinatsu Arima, Seiichi Kato, Shuta Tomida, Motoshi Suzuki, Hirotaka Osada, Takashi Takahashi

研究成果: Article査読

163 被引用数 (Scopus)

抄録

We and others previously identified NKX2-1, also known as TITF1 and TTF-1, as a lineage-survival oncogene in lung adenocarcinomas. Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation. Notably, ROR1 knockdown effectively inhibited lung adenocarcinoma cell lines, irrespective of their EGFR status, including those with resistance to the EGFR tyrosine kinase inhibitor gefitinib. Our findings thus identify ROR1 as an " Achilles' heel" in lung adenocarcinoma, warranting future development of therapeutic strategies for this devastating cancer.

本文言語English
ページ(範囲)348-361
ページ数14
ジャーナルCancer Cell
21
3
DOI
出版ステータスPublished - 20-03-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 細胞生物学
  • 癌研究

フィンガープリント

「NKX2-1/TITF1/TTF-1-Induced ROR1 Is Required to Sustain EGFR Survival Signaling in Lung Adenocarcinoma」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