Oncotarget

Research Papers:

IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma

Ling Gao, Xiaolong Wang, Xiaofei Wang, Linmei Zhang, Cui Qiang, Su’e Chang, Wenhao Ren, Shaoming Li, Yang Yang, Dongdong Tong, Cheng Chen, Zongfang Li, Tusheng Song, Keqian Zhi and Chen Huang _

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Oncotarget. 2014; 5:2562-2574. https://doi.org/10.18632/oncotarget.1812

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Abstract

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

Correspondence:

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

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.


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