Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling
DOI
10.3390/biom11020183
Document Type
Journal Article
Publication Date
1-29-2021
Publication Title
Biomolecules
Volume
11
Issue
2
Keywords
EMT, ERK5, cancer metastases, therapy
Abstract
Extracellular signal-regulated kinase (ERK5) is an essential regulator of cancer progression, tumor relapse, and poor patient survival. Epithelial to mesenchymal transition (EMT) is a complex oncogenic process, which drives cell invasion, stemness, and metastases. Activators of ERK5, including mitogen-activated protein kinase 5 (MEK5), tumor necrosis factor α (TNF-α), and transforming growth factor-β (TGF-β), are known to induce EMT and metastases in breast, lung, colorectal, and other cancers. Several downstream targets of the ERK5 pathway, such as myocyte-specific enhancer factor 2c (MEF2C), activator protein-1 (AP-1), focal adhesion kinase (FAK), and c-Myc, play a critical role in the regulation of EMT transcription factors SNAIL, SLUG, and β-catenin. Moreover, ERK5 activation increases the release of extracellular matrix metalloproteinases (MMPs), facilitating breakdown of the extracellular matrix (ECM) and local tumor invasion. Targeting the ERK5 signaling pathway using small molecule inhibitors, microRNAs, and knockdown approaches decreases EMT, cell invasion, and metastases via several mechanisms. The focus of the current review is to highlight the mechanisms which are known to mediate cancer EMT via ERK5 signaling. Several therapeutic approaches that can be undertaken to target the ERK5 pathway and inhibit or reverse EMT and metastases are discussed.
Open Access
OA
Preprint
Repository Citation
Bhatt, A. B., Patel, S., Matossian, M. D., Ucar, D. A., Miele, L., Burow, M. E., Flaherty, P. T., & Cavanaugh, J. E. (2021). Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling. Biomolecules, 11 (2). https://doi.org/10.3390/biom11020183