TY  - JOUR
A1  - Paudel, Rupesh
A1  - Fusi, Lorenza
A1  - Schmidt, Marc
T1  - The MEK5/ERK5 pathway in health and disease
T2  - International Journal of Molecular Sciences
N2  - The MEK5/ERK5 mitogen-activated protein kinases (MAPK) cascade is a unique signaling module activated by both mitogens and stress stimuli, including cytokines, fluid shear stress, high osmolarity, and oxidative stress. Physiologically, it is mainly known as a mechanoreceptive pathway in the endothelium, where it transduces the various vasoprotective effects of laminar blood flow. However, it also maintains integrity in other tissues exposed to mechanical stress, including bone, cartilage, and muscle, where it exerts a key function as a survival and differentiation pathway. Beyond its diverse physiological roles, the MEK5/ERK5 pathway has also been implicated in various diseases, including cancer, where it has recently emerged as a major escape route, sustaining tumor cell survival and proliferation under drug stress. In addition, MEK5/ERK5 dysfunction may foster cardiovascular diseases such as atherosclerosis. Here, we highlight the importance of the MEK5/ERK5 pathway in health and disease, focusing on its role as a protective cascade in mechanical stress-exposed healthy tissues and its function as a therapy resistance pathway in cancers. We discuss the perspective of targeting this cascade for cancer treatment and weigh its chances and potential risks when considering its emerging role as a protective stress response pathway.
KW  - atherosclerosis
KW  - bone
KW  - cartilage
KW  - endothelium
KW  - extracellular-regulated kinase 5
KW  - Krüppel-like factor
KW  - mechanotransduction
KW  - mitogen-activated protein kinase
KW  - stress signaling
KW  - tumor
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/26163
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-261638
SN  - 1422-0067
VL  - 22
IS  - 14
ER  -