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

Wang, Zhi Gang and Fukazawa, Takuya and Nishikawa, Toshio and Watanabe, Nobuyuki and Sakurama, Kazufumi and Motoki, Takayuki and Takaoka, Munenori and Hatakeyama, Shinji and Omori, Osamu and Ohara, Toshiaki and Tanabe, Shunsuke and Fujiwara, Yasuhiro and Shirakawa, Yasuhiro and Yamatsuji, Tomoki and Tanaka, Noriaki and Naomoto, Yoshio (2008) TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncology Reports, 20 (6). pp. 1473-1477. ISSN 1021-335X

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.

Item Type: Article
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Date Deposited: 14 Dec 2009 13:48
Last Modified: 31 Jan 2013 00:54
URI: https://oak.novartis.com/id/eprint/1422

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