RhoC mediates epidermal growth factor-stimulated migration and invasion in head and neck squamous cell carcinoma.
RhoC mediates epidermal growth factor-stimulated migration and invasion in head and neck squamous cell carcinoma.
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DOI：
10.1016/j.neo.2014.12.002
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发表时间：
2015-01
期刊：
影响因子：
4.8
通讯作者：
Henson, Bradley S.
中科院分区：
文献类型：
--
作者：
Tumur, Zohra;Katebzadeh, Shahbaz;Guerra, Carlos;Bhushan, Lokesh;Alkam, Tursun;Henson, Bradley S.
表皮生长因子受体 (EGFR) 在头颈鳞状细胞癌 (HNSCC) 中过度表达，已被证明磷酸化后可促进肿瘤细胞侵袭。 EGFR 促进肿瘤进展的一种机制是通过激活信号级联，导致 E-钙粘蛋白（一种细胞与细胞粘附连接的跨膜糖蛋白）的丢失。然而，这些信号级联的中介者尚未完全了解。其中一种介质 RhoC 在许多外部刺激（例如表皮生长因子 (EGF)）下被激活，但其作为 EGF 刺激的迁移和侵袭介质的作用在 HNSCC 中尚未阐明。在本研究中，我们研究了 RhoC 作为 EGF 刺激的 HNSCC 迁移和侵袭介质的作用。我们发现，在 EGF 刺激后，EGFR 和 RhoC 在 HNSCC 中被强烈激活。这导致磷脂酰肌醇 3-激酶 Akt 通路 (PI3K-Akt) 的激活、GSK-3β 在 Ser9 残基处的磷酸化，以及随后 E-钙粘蛋白细胞表面表达的下调，导致肿瘤细胞侵袭增加。 RhoC 的敲低可恢复 E-钙粘蛋白的表达并抑制 EGF 刺激的迁移和侵袭。这是 HNSCC 中第一份报告，证明 RhoC 通过下调 PI3K-Akt 通路和 E-钙粘蛋白表达，在介导 EGF 刺激的迁移和侵袭中发挥作用。 RhoC 可能作为 HNSCC 的治疗靶点。
Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where it has been shown to promote tumor cell invasion upon phosphorylation. One mechanism by which EGFR promotes tumor progression is by activating signal cascades that lead to loss of E-cadherin, a transmembrane glycoprotein of the cell-cell adherence junctions; however mediators of these signaling cascades are not fully understood. One such mediator, RhoC, is activated upon a number of external stimuli, such as epidermal growth factor (EGF), but its role as a mediator of EGF-stimulated migration and invasion has not been elucidated in HNSCC. In the present study, we investigate the role of RhoC as a mediator of EGF-stimulated migration and invasion in HNSCC. We show that upon EGF stimulation, EGFR and RhoC were strongly activated in HNSCC. This resulted in activation of the phosphatidylinositol 3-Kinase Akt pathway (PI3K-Akt), phosphorylation of GSK-3β at the Ser9 residue, and subsequent down regulation of E-cadherin cell surface expression resulting in increased tumor cell invasion. Knockdown of RhoC restored E-cadherin expression and inhibited EGF-stimulated migration and invasion. This is the first report in HNSCC demonstrating the role RhoC plays in mediating EGF-stimulated migration and invasion by down-regulating the PI3K-Akt pathway and E-cadherin expression. RhoC may serve as a treatment target for HNSCC.
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DOI：
10.1016/s1044-0305(03)00206-x
发表时间：
2003-09-01
影响因子：
3.2
作者：
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影响因子：
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作者：
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影响因子：
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DOI：
10.1158/1541-7786.mcr-08-0512
发表时间：
2009-11
期刊：
Molecular cancer research : MCR
影响因子：
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Islam M;Lin G;Brenner JC;Pan Q;Merajver SD;Hou Y;Kumar P;Teknos TN
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