Erk1/2 activatiOn and modulation of STAT3 signaling in oral cancer
Erk1/2 activatiOn and modulation of STAT3 signaling in oral cancer
复制标题
DOI：
10.3892/or.2014.3440
复制
发表时间：
2014-11-01
期刊：
影响因子：
4.2
通讯作者：
Sklavounou, Alexandra
中科院分区：
文献类型：
--
作者：
Gkouveris, Ioannis;Nikitakis, Nikolaos;Sklavounou, Alexandra
信号转导子和转录激活子3（STAT 3）信号通路的组成性激活在口腔鳞状细胞癌（OSCC）中具有致癌潜力。与其他分子途径的串扰有助于癌症中的STAT 3调节。丝裂原活化蛋白激酶（MAPK），特别是细胞外信号调节激酶1/2（Erk 1/2）对STAT 3信号在口腔鳞癌中的作用尚未得到彻底研究。本研究探讨Erk 1/2调控对口腔鳞癌细胞中STAT 3信号和细胞生长的影响。在OSCC细胞系中评估磷酸化（酪氨酸和丝氨酸）和总STAT 3、Erk 1/2和细胞周期蛋白D1的组成型表达水平。Erk 1/2调节通过药理学试剂实现;还进行了针对Erk 1/2的siRNA沉默。评估细胞增殖和活力。U 0126处理或特异性siRNA沉默对Erk 1/2的抑制导致OSCC细胞中p-ser STAT 3和cyclin D1水平的降低和p-tyr STAT 3水平的增加。此外，Erk 1/2抑制导致OSCC细胞生长和活力的剂量依赖性降低。Erk 1/2诱导具有相反的效果。综上所述，这些结果支持了OSCC中致癌Erk 1/2和STAT 3通路之间的主动串扰，其意义需要进一步研究。
Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway possesses confirmed oncogenic potential in oral squamous cell carcinoma (OSCC). Crosstalk with other molecular pathways contributes to STAT3 regulation in cancer. The effects of mitogen-activated protein kinases (MAPKs) and particularly extracellular signal-regulated kinase 1/2 (Erk1/2) on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examined the effects of Erk1/2 modulation on STAT3 signaling and cell growth in OSCC cells. Constitutive expression levels of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2 and cyclin D1 were assessed in OSCC cell lines. Erk1/2 modulation was achieved by pharmacological agents; siRNA silencing against Erk1/2 was also performed. Cell proliferation and viability were assessed. Erk1/2 inhibition with either U0126 treatment or specific siRNA silencing resulted in decreases in p-ser STAT3 and cyclin D1 levels and increases in p-tyr STAT3 in OSCC cells. Moreover, Erk1/2 inhibition resulted in a dose-dependent reduction in OSCC cell growth and viability. Erk1/2 induction had the opposite effects. Taken together, these results are supportive of an active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC, the significance of which requires further investigation.