IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma
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Ling Gao1,2, Xiaolong Wang1, Xiaofei Wang2, Linmei Zhang1, Cui Qiang1, Su’e Chang2, Wenhao Ren1, Shaoming Li1, Yang Yang2, Dongdong Tong2, Cheng Chen1, Zongfang Li3, Tusheng Song2, Keqian Zhi1, Chen Huang2
1 Department of Oral Maxillofacial Surgery, Stomatology Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, P. R. China
2 Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
3 Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, P. R. China
Chen Huang, email:
Keqian Zhi, email:
Keywords: oral squamous cell carcinoma; IGF-1R; IRS-2; let-7b; proliferation
Received: January 8, 2014 Accepted: March 19, 2014 Published: March 21, 2014
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.
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