TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells

Zhi Gang Wang, Takuya Fukazawa, Toshio Nishikawa, Nobuyuki Watanabe, Kazufumi Sakurama, Takayuki Motoki, Munenori Takaoka, Shinji Hatakeyama, Osamu Omori, Toshiaki Ohara, Shunsuke Tanabe, Yasuhiro Fujiwara, Yasuhiro Shirakawa, Tomoki Yamatsuji, Noriaki Tanaka, Yoshio Naomoto

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Esophageal cancer is one of the most aggressive cancers in the world. Novel preventive and therapeutic strategies tend to target the key molecules involved in the signaling transduction pathways for cell growth. It is known that FAK and mTOR are important controllers of cell growth. TAE226, a novel small molecule compound, is a potent ATP competitive inhibitor of FAK and IGF-IR. TAE226 can block FAK and IGF-IR signaling pathways. The purpose of this study was to explore the inhibitory effects on mTOR signaling and the mechanism of cell growth suppression by TAE226. We examined the expression of mTOR and S6 in esophageal cancer cells (SEG-1) and normal esophageal epithelial cells (KOB-13) and the efficacy of TAE226 against SEG-1 cells. mTOR and S6 were overexpressed in SEG-1 cells compared with KOB-13 cells. TAE226 inhibited the expression of mTOR, Akt, p70S6K and S6 as well as the phosphorylation of mTOR (Ser2448), Akt (Ser473), p70S6K (Thr389) and S6 (Ser240/244). As a result, TAE226 induced a dose-dependent decrease in cell growth (number) and damage in the cell shape. Together, these data show that TAE226 has potent inhibitory effects on mTOR signaling and esophageal cancer cell growth indicating that TAE226 has potential application in esophageal cancer treatment.

Original languageEnglish
Pages (from-to)1473-1477
Number of pages5
JournalOncology reports
Volume20
Issue number6
DOIs
Publication statusPublished - 2008

Keywords

  • Cell growth
  • Esophageal cancer
  • MTOR signaling
  • TAE226

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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