title: Insulin-like growth factor 1 promotes growth of gastric cancer by inhibiting foxo1 nuclear retention.
abstract: Gastric cancer (GC) is the fourth most common malignant human cancer. So far, the molecular mechanisms underlying the tumorigenesis of GC are not completely understood. Here, we reported significantly higher levels of serum insulin-like growth factor (IGF)-1 in GC patients and significantly higher levels of phosphorylated IGF-1 receptor (IGF-1R) in the GC specimen. Moreover, IGF-1 induced phosphorylation of IGF-1R and then phosphorylation of its downstream factor Akt in the GC cells. Further, IGF-1/Akt-induced forkhead box protein O1 (FoxO1) nuclear exclusion, but not IGF-1/Akt-induced mTOR phosphorylation, was essential for the augment in GC cell growth. Together, IGF-1/Akt/FoxO1 regulatory machinery appears to be a previously unappreciated signaling axis involved in the carcinogenesis of GC.
authors.affiliation: Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, 250014, China.
authors.forename: Shuangling
authors.initials: S
authors.lastname: Li
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Lei
authors.forename: Jianna
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongli
authors.initials: H
authors.lastname: Yang
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases