Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner.
Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner.
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细胞外信号调节激酶5以FAK依赖性方式促进细胞迁移、侵袭和肺转移。
DOI：
10.1007/s13238-020-00701-1
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发表时间：
2020-11
期刊：
影响因子：
21.1
通讯作者：
Hua ZC
中科院分区：
文献类型：
--
作者：
Jiang W;Cai F;Xu H;Lu Y;Chen J;Liu J;Cao N;Zhang X;Chen X;Huang Q;Zhuang H;Hua ZC
本研究旨在评估肺癌和恶性黑色素瘤进展中ERK 5的表达，并确定ERK 5信号转导在肺癌和黑色素瘤中的参与。我们发现ERK 5在人肺癌样本中表达丰富，并且肺癌中ERK 5表达升高与获得增加的转移和侵袭潜力有关。重要的是，我们观察到ERK 5活性和FAK表达及其在Ser 910位点的磷酸化之间存在显著相关性。从机制上讲，ERK 5增加了转录因子USF 1的表达，USF 1可以转录上调FAK的表达，导致FAK信号转导激活，促进细胞迁移。我们还提供了证据表明，FAK在Ser 910的磷酸化是由于ERK 5，而不是ERK 1/2，然后我们提出了Ser 910在控制细胞运动中的作用。此外，ERK 5除了FAK之外还有调节癌细胞中上皮向间充质转化和细胞运动的靶点。总之，我们的研究结果揭示了ERK 5的癌症转移促进作用，并为靶向ERK 5作为潜在的治疗方法提供了理论基础。本文的在线版本（10.1007/s13238-020-00701-1）包含补充材料，可供授权用户使用。
This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential. Importantly, we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser910 site. Mechanistically, ERK5 increased the expression of the transcription factor USF1, which could transcriptionally upregulate FAK expression, resulting in FAK signaling activation to promote cell migration. We also provided evidence that the phosphorylation of FAK at Ser910 was due to ERK5 but not ERK1/2, and we then suggested a role for Ser910 in the control of cell motility. In addition, ERK5 had targets in addition to FAK that regulate epithelial-to-mesenchymal transition and cell motility in cancer cells. Taken together, our findings uncover a cancer metastasis-promoting role for ERK5 and provide the rationale for targeting ERK5 as a potential therapeutic approach. The online version of this article (10.1007/s13238-020-00701-1) contains supplementary material, which is available to authorized users.
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影响因子：
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通讯作者：
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