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

被引：49

作者：

Gao, Ling ^{[1
,2
]}

Wang, Xiaolong ^{[1
]}

Wang, Xiaofei ^{[2
]}

Zhang, Linmei ^{[1
]}

Qiang, Cui ^{[1
]}

Chang, Su'e ^{[2
]}

Ren, Wenhao ^{[1
]}

Li, Shaoming ^{[1
]}

Yang, Yang ^{[2
]}

Tong, Dongdong ^{[2
]}

Chen, Cheng ^{[1
]}

Li, Zongfang ^{[3
]}

Song, Tusheng ^{[2
]}

Zhi, Keqian ^{[1
]}

Huang, Chen ^{[2
]}

机构：

[1] Xi An Jiao Tong Univ, Coll Med, Dept Oral Maxillofacial Surg, Stomatol Hosp, Xian 710049, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Coll Med, Key Lab Environm & Genes Related Dis, Xian 710049, Shaanxi, Peoples R China

[3] Xi An Jiao Tong Univ, Sch Med, Dept Gen Surg, Affiliated Hosp 2, Xian 710049, Shaanxi, Peoples R China

来源：

ONCOTARGET | 2014年 / 5卷 / 09期

关键词：

oral squamous cell carcinoma; IGF-1R; IRS-2; let-7b; proliferation; CANCER; MICRORNA; RECEPTOR; GROWTH; ACTIVATION; ERK; PHOSPHORYLATION; INTEGRATION; INHIBITION; EXPRESSION;

D O I：

10.18632/oncotarget.1812

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：2562 / 2574

页数：13

共 51 条

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