title: TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells.
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.
authors.affiliation: College of Life Science, Inner Mongolia University, The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Huhhot 010021, P.R. China.
authors.forename: Zhi Gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Sakurama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Motoki
authors.forename: Munenori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Omori
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohara
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shirakawa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamatsuji
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; C524632:TAE226; D011494:Protein Kinases; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases