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首页> 外文期刊>Clinical and Translational Medicine >Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
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Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses

机译:骨桥蛋白在人肺癌细胞上皮对间充质转换和反应的调节作用

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Background Lung cancer is still the main cause of death in patients with cancer, due to poor understanding of intracellular regulations. Of those, osteopontin (OPN) may induce the epithelial‐to‐mesenchymal transition (EMT) to promote tumor cell metastasis. The present study aims to evaluate the regulatory mechanism of internal and external OPN in the development of lung cancer. Methods We evaluated genetic variations and different bioinformatics of genes in chromosome 4 among subtypes of lung cancer using global databases. We validated the expression of OPN and EMT‐related proteins (e.g., E‐cadherin, vimentin) in 208 non‐small‐cell lung cancer (NSCLC) tumors and the adjacent nontumorous tissues, further to explore the function of OPN in the progression of lung cancer, with a focus on a potential communication between OPN and EMT in the lung cancer. Results We found that OPN might act as a target molecule in lung cancer, which is associated with lymph node metastasis, postresection recurrence/metastasis, and prognosis of patients with lung cancer. Biological behaviors and pathological responses of OPN varied among diseases, challenges, and severities. Overexpression of OPN was correlated with the existence of EMT in lung cancer tissues. Internal and external OPN plays the decisive roles in lung cancer cell movement, proliferation, and EMT formation, through the upregulation of OPN‐PI3K and OPN‐MEK pathways. PI3K and MEK inhibitors downregulated the process of EMT and biological behaviors of lung cancer cells, probably through altering vimentin‐associated cytoskeletons. Conclusion OPN can be a metastasis‐associated or specific biomarker for lung cancer and a potential target for antimetastatic treatment.
机译:由于对细胞内法规的理解差,因此肺癌仍然是癌症患者死亡的主要原因。其中,Osteopontin(OPN)可以诱导上皮 - 间充质转变(EMT)以促进肿瘤细胞转移。本研究旨在评估内外opn在肺癌发展中的监管机制。方法使用全球数据库评估肺癌亚型中4种染色体4中基因的遗传变异和不同生物信息。我们经过验证了OPN和EMT相关蛋白(例如,E-CADERIN,Vimentin)在208例非小细胞肺癌(NSCLC)肿瘤和相邻的不初始组织中表达,进一步探讨了OPN在进展中的功能肺癌,重点关注肺癌的OPN和EMT之间的潜在通信。结果我们发现OPN可以作为肺癌中的目标分子,与淋巴结转移,肺癌患者的淋巴结转移和预后相关。 opn的生物行为和病理反应在疾病,挑战和严重程度之间变化。 OPN的过度表达与肺癌组织中EMT的存在相关。内部和外部OPN通过OPN-PI3K和OPN-MEK途径的上调,起到肺癌细胞运动,增殖和EMT形成中的决定性作用。 PI3K和MEK抑制剂下调了肺癌细胞EMT和生物学行为的过程,可能是通过改变Vimentin相关的细胞骨架。结论OPN可以是肺癌的转移相关或特异性生物标志物和抗致抗体治疗的潜在目标。

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