Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner

Weiwei Jiang, Fangfang Cai, Huangru Xu, Yanyan Lu, Jia Chen, Jia Liu, Nini Cao, Xiangyu Zhang, Xiao Chen, Qilai Huang, Hongqin Zhuang*, Zi Chun Hua

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)825-845
Number of pages21
JournalProtein and Cell
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2020
Externally publishedYes

Keywords

  • EMT
  • ERK5
  • FAK
  • USF1
  • lung cancer
  • melanoma
  • metastasis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

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