The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion.
Telfer, Brian A
Pearson, Adam J
Finegan, Katherine G; orcid: 0000-0003-2885-0122
Giurisato, Emanuele; orcid: 0000-0003-0598-6449
Tournier, Cathy; orcid: 0000-0002-4618-2570; email: firstname.lastname@example.org
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AbstractThere is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Mechanistically, our in vitro data revealed that ERK5 was critical for maintaining the invasive capability of triple-negative breast cancer (TNBC) cells through focal adhesion protein kinase (FAK) activation. Specifically, we found that phosphorylation of FAK at Tyr397 was controlled by a kinase-independent function of ERK5. Accordingly, silencing ERK5 in mammary tumor grafts impaired FAK phosphorylation at Tyr397 and suppressed TNBC cell metastasis to the lung without preventing tumor growth. Collectively, these results establish a functional relationship between ERK5 and FAK signaling in promoting malignancy. Thus, targeting the oncogenic ERK5-FAK axis represents a promising therapeutic strategy for breast cancer exhibiting aggressive clinical behavior.
DescriptionFrom PubMed via Jisc Publications Router
History: received 2020-04-21, revised 2021-03-23, accepted 2021-04-14
Publication status: aheadofprint
Funder: RCUK | MRC | Medical Research Foundation; Grant(s): MC_PC_18056
Funder: Worldwide Cancer Research; Grant(s): 15-1283