IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma.
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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IGF-1R 是 let-7b 的靶标，介导 IRS-2/Akt 和 MAPK 通路之间的串扰，促进口腔鳞状细胞癌的增殖
DOI：
10.18632/oncotarget.1812
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发表时间：
2014-05-15
期刊：
影响因子：
--
通讯作者：
Huang C
中科院分区：
文献类型：
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作者：
Gao L;Wang X;Wang X;Zhang L;Qiang C;Chang S;Ren W;Li S;Yang Y;Tong D;Chen C;Li Z;Song T;Zhi K;Huang C
胰岛素样生长因子（Insulin-like growth factor，IGF）信号通路参与口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）的发生发展，但IGF-1受体（IGF-1 R）介导的复杂的分子调控网络和信号通路尚不清楚。在这里，我们发现IGF-1 R和胰岛素受体底物-2（IRS-2）的过度表达与组织分化呈负相关。IGF信号刺激OSCC细胞生长。相反，let-7 b过表达抑制增殖和集落形成，并通过Akt途径靶向IGF-1 R和IRS-2触发S/G2细胞周期阻滞。此外，let-7 b和IGF-1 R/IRS-2的表达之间的负相关关系在OSCC肿瘤异种移植物和临床标本中得到证实。此外，通过激活ERK 1/2，IGF-1 R转录上调IRS-2。我们的研究结果表明，let-7 b/IGF-1 R介导的IRS-2/Akt和MAPK之间的串扰参与了OSCC，是一个潜在的治疗靶点。
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.