@article{086c7e87ec3945b79e82d65ffd7e9096,
title = "Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner",
abstract = "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.",
keywords = "EMT, ERK5, FAK, USF1, lung cancer, melanoma, metastasis",
author = "Weiwei Jiang and Fangfang Cai and Huangru Xu and Yanyan Lu and Jia Chen and Jia Liu and Nini Cao and Xiangyu Zhang and Xiao Chen and Qilai Huang and Hongqin Zhuang and Hua, {Zi Chun}",
note = "Funding Information: This study was supported by grants from the Chinese National Natural Sciences Foundation (81773099, 81570790), the National Key R&D Program of China (2017YFA0506000). Weiwei Jiang, Fangfang Cai, Huangru Xu, Yanyan Lu, Jia Chen, Jia Liu, Nini Cao, Xiangyu Zhang, Xiao Chen, Qilai Huang, Hongqin Zhuang and Zi-Chun Hua declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed. ZCH and HZ designed the outline of the paper. HZ wrote the manuscript. WJ and FC contributed equally to this work. WJ and FC performed most experiments in this study and prepared the figures. NC, XZ, JC and YL performed the experiments with the animals. HX, JL and XC helped with the western bolt experiments. QH constructed gene reporter plasmids. HZ and WJ analyzed data. All authors have read and approved the final version of this manuscript. Funding Information: This study was supported by grants from the Chinese National Natural Sciences Foundation (81773099, 81570790), the National Key R&D Program of China (2017YFA0506000). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = nov,
day = "1",
doi = "10.1007/s13238-020-00701-1",
language = "English (US)",
volume = "11",
pages = "825--845",
journal = "Protein and Cell",
issn = "1674-800X",
publisher = "Springer-Verlag GmbH and Co. KG",
number = "11",
}
