Fangfang Cai
Huangru Xu
Yanyan Lu
Jia Chen
Jia Liu
Nini Cao
Xiangyu Zhang
Xiao Chen
Qilai Huang
Hongqin Zhuang
Zi-Chun Hua
1 The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing 210023, China;
2 Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, China
Funds: This study was supported by grants from the Chinese National Natural Sciences Foundation (81773099, 81570790), the National Key R&D Program of China (2017YFA0506000).
Received Date: 2019-12-03
Rev Recd Date:2020-02-09
Abstract
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: ERK5,
lung cancer,
melanoma,
metastasis,
FAK,
USF1,
EMT
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