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.

journal_name

Protein Cell

journal_title

Protein & cell

authors

Jiang W,Cai F,Xu H,Lu Y,Chen J,Liu J,Cao N,Zhang X,Chen X,Huang Q,Zhuang H,Hua ZC

doi

10.1007/s13238-020-00701-1

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

825-845

issue

11

eissn

1674-800X

issn

1674-8018

pii

10.1007/s13238-020-00701-1

journal_volume

11

pub_type

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