ERK5 is activated by oncogenic BRAF and promotes melanoma growth

Oncogene
Ignazia TusaElisabetta Rovida

Abstract

Malignant melanoma is among the most aggressive cancers and its incidence is increasing worldwide. Targeted therapies and immunotherapy have improved the survival of patients with metastatic melanoma in the last few years; however, available treatments are still unsatisfactory. While the role of the BRAF-MEK1/2-ERK1/2 pathway in melanoma is well established, the involvement of mitogen-activated protein kinases MEK5-ERK5 remains poorly explored. Here we investigated the function of ERK5 signaling in melanoma. We show that ERK5 is consistently expressed in human melanoma tissues and is active in melanoma cells. Genetic silencing and pharmacological inhibition of ERK5 pathway drastically reduce the growth of melanoma cells and xenografts harboring wild-type (wt) or mutated BRAF (V600E). We also found that oncogenic BRAF positively regulates expression, phosphorylation, and nuclear localization of ERK5. Importantly, ERK5 kinase and transcriptional transactivator activities are enhanced by BRAF. Nevertheless, combined pharmacological inhibition of BRAFV600E and MEK5 is required to decrease nuclear ERK5, that is critical for the regulation of cell proliferation. Accordingly, combination of MEK5 or ERK5 inhibitors with BRAFV600E inhib...Continue Reading

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Citations

Feb 7, 2020·International Journal of Molecular Sciences·Adam J PearsonCathy Tournier
Sep 12, 2020·Biochemical Society Transactions·Simon J CookPamela A Lochhead
Mar 25, 2019·International Journal of Molecular Sciences·Barbara Stecca, Elisabetta Rovida
Feb 7, 2020·International Journal of Molecular Sciences·Alessandro TubitaElisabetta Rovida
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Apr 25, 2020·International Journal of Molecular Sciences·Lucia MagnelliLaura Papucci
Mar 6, 2019·Cancer Research·Lucía Benito-JardónJoaquin Teixidó
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Mar 18, 2021·European Journal of Medicinal Chemistry·Seungbeom LeeHwayoung Yun
Mar 30, 2021·Frontiers in Cell and Developmental Biology·Alessandro TubitaElisabetta Rovida
Jul 25, 2021·International Journal of Molecular Sciences·Rupesh PaudelMarc Schmidt
May 8, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alessandra GentiliniFabio Marra
Oct 17, 2021·Journal of Cellular and Molecular Medicine·Marta Ortega-MuelasRicardo Sánchez-Prieto
May 8, 2020·The Journal of Investigative Dermatology·Christian AdamMarc Schmidt

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Methods Mentioned

BETA
nuclear translocation
xenograft
xenografts
transfection
PCR
flow cytometry
Assay

Software Mentioned

Adobe Photoshop

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