title: IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma.
abstract: Insulin-like growth factor (IGF) signaling is involved in oral squamous cell carcinoma (OSCC), but IGF-1 receptor (IGF-1R)-mediated intricate regulatory networks among molecular interactions and signalling path ways in OSCC remain unclear. Here, we found that overexpression of IGF-1R and insulin receptor substrate-2 (IRS-2) was negatively associated with histological differentiation. IGF signaling stimulated OSCC cell growth. Conversely, overexpression of let-7b inhibited proliferation and colony formation and triggered S/G2 cell cycle arrest by targeting IGF-1R and IRS-2 through the Akt pathway. Also, the inverse relationship between expression of let-7b and IGF-1R/IRS-2 was conﬁrmed in OSCC tumor xenografts and clinical specimens. Furthermore, by activating ERK1/2, IGF-1R transcriptionally upregulated IRS-2. Our results indicate that let-7b/IGF-1R-mediated crosstalk between IRS-2/Akt and MAPK is involved in OSCC and is a potential therapeutic target for therapy.
authors.affiliation: Department of Oral Maxillofacial Surgery, Stomatology Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Linmei
authors.initials: L
authors.lastname: Zhang
authors.forename: Cui
authors.initials: C
authors.lastname: Qiang
authors.forename: Su'e
authors.initials: S
authors.lastname: Chang
authors.forename: Wenhao
authors.initials: W
authors.lastname: Ren
authors.forename: Shaoming
authors.initials: S
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Dongdong
authors.initials: D
authors.lastname: Tong
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.forename: Keqian
authors.initials: K
authors.lastname: Zhi
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D055504:Insulin Receptor Substrate Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases