@article{10902/36664,
year = {2025},
url = {https://hdl.handle.net/10902/36664},
abstract = {ERK1/2 mitogen-activated protein kinases (ERK) are key regulators of basic cellular processes, including proliferation, survival, and migration. Upon phosphorylation, ERK becomes activated and a portion of it dimerizes. The importance of ERK activation in specific cellular events is generally well documented, but the role played by dimerization is largely unknown. Here, we demonstrate that impeding ERK dimerization precludes cellular movement by interfering with the molecular machinery that executes the rearrangements of the actin cytoskeleton. We also show that a constitutively dimeric ERK mutant can drive cell motility per se, demonstrating that ERK dimerization is both necessary and sufficient for inducing cellular migration. Importantly, we unveil that the scaffold protein kinase suppressor of Ras 1 (KSR1) is a critical element for endowing external agonists, acting through tyrosine kinase receptors, with the capacity to induce ERK dimerization and, subsequently, to unleash cellular motion. In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination.},
organization = {We are indebted to Dr D. Engelberg for providing
reagents. PC lab is supported by grant PID2021-
126288OB-I00 and PDC2022-133569-I00 from the
Spanish Ministry of Science (MICIU/AEI/FEDER,
UE); CIBERONC (CB16/12/00436) from the Instituto
de Salud Carlos III (ISCIII); and a grant from ASPLA
S.A “Encintalo en Rosa” Initiative. BC is funded by
grants from Ministerio de Innovación, Ciencia y Universidades,
MICIU PID2020/112760RB-100 and La
Fundació d’Estudis i Recerca Oncológica (FERO,
BFERO2021.03). JA is supported by CIBERONC;
Breast Cancer Research Foundation (BCRF-23-008) and Instituto de Salud Carlos III (ISCIII) (PI22/ 00001). AK is supported by the Wellcome Trust (Multiuser
Equipment Grant, 208402/Z/17/Z). DF-V is a
CIBERONC predoctoral fellow (JCSTF2105526).},
publisher = {John Wiley & Sons},
publisher = {Molecular Oncology, 2025, 19(2), 452-473},
title = {ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility},
author = {De la Fuente Vivas, Dalia and Cappitelli, Vincenzo and García Gómez, Rocío and Valero Díaz, Sara and Amato, Camilla and Rodríguez, Javier and Duro-Sánchez, Santiago and Kriegsheim, Alexander von and Grusch, Michael and Lozano, José and Arribas, Joaquín and Casar Martínez, Berta and Crespo, Piero},
}