TY - JOUR
T1 - COX2 expression and Erk1/Erk2 activity mediate Cot-induced cell migration
AU - Rodriguez, Cristina
AU - Lopez, Pilar
AU - Pozo, Maite
AU - Duce, Antonio Martin
AU - Lopez Pelaez, Marta
AU - Fernandez, Margarita
AU - Alemany, Susana
PY - 2008/9
Y1 - 2008/9
N2 - The MAPKKK8 Cot/tpl-2, identified as an oncogene (Cot-T), participates in the intracellular signaling activated by members of the TLR and TNF alpha receptor superfamilies. Here we demonstrate that Cot promotes cell migration by regulating different steps involved in this process, such as cell adhesion and metalloproteinase activity. Indeed, Cot also regulates the cytoskeleton and Cot-T overexpression provokes the polarization of microtubules and the loss of stress fibers. Moreover, and in accordance with the increased Rac-GTP levels observed, Cot-T overexpressing cells develop more lamellipodia than control cells. Conversely, depletion of endogenous Cot increases the formation of stress fibers which is correlated with the high levels of Rho-GTP observed in these cells. In addition, the increase in COX2 expression and the activation of Erk1/2 regulated by Cot are essential for the induction of cell migration. Together, these data provide evidence of a new role for both proto-oncogenic and oncogenic Cot. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.
AB - The MAPKKK8 Cot/tpl-2, identified as an oncogene (Cot-T), participates in the intracellular signaling activated by members of the TLR and TNF alpha receptor superfamilies. Here we demonstrate that Cot promotes cell migration by regulating different steps involved in this process, such as cell adhesion and metalloproteinase activity. Indeed, Cot also regulates the cytoskeleton and Cot-T overexpression provokes the polarization of microtubules and the loss of stress fibers. Moreover, and in accordance with the increased Rac-GTP levels observed, Cot-T overexpressing cells develop more lamellipodia than control cells. Conversely, depletion of endogenous Cot increases the formation of stress fibers which is correlated with the high levels of Rho-GTP observed in these cells. In addition, the increase in COX2 expression and the activation of Erk1/2 regulated by Cot are essential for the induction of cell migration. Together, these data provide evidence of a new role for both proto-oncogenic and oncogenic Cot. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.
U2 - 10.1016/j.cellsig.2008.05.008
DO - 10.1016/j.cellsig.2008.05.008
M3 - Article
C2 - 18572386
SN - 0898-6568
VL - 20
SP - 1625
EP - 1631
JO - Cellular Signalling
JF - Cellular Signalling
IS - 9
ER -