IGF-1R, a Target of Let-7b, Mediates Crosstalk Between IRS-2/Akt and MAPK Pathways to Promote Proliferation of Oral Squamous Cell Carcinoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 May 10

PMID 24810113

Citations 29

Authors

Ling Gao

Xiaolong Wang

Xiaofei Wang

Linmei Zhang

Cui Qiang

Sue Chang

Wenhao Ren

Shaoming Li

Yang Yang

Dongdong Tong

Cheng Chen

Zongfang Li

Tusheng Song

Keqian Zhi

Chen Huang

Affiliations

Soon will be listed here.

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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