COX2 expression and Erk1/Erk2 activity mediate Cot-induced cell migration

Cristina Rodriguez, Pilar Lopez, Maite Pozo, Antonio Martin Duce, Marta Lopez Pelaez, Margarita Fernandez, Susana Alemany

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1625-1631
    Number of pages7
    JournalCellular Signalling
    Volume20
    Issue number9
    DOIs
    Publication statusPublished - Sep 2008

    Cite this

    Rodriguez, C., Lopez, P., Pozo, M., Duce, A. M., Lopez Pelaez, M., Fernandez, M., & Alemany, S. (2008). COX2 expression and Erk1/Erk2 activity mediate Cot-induced cell migration. Cellular Signalling, 20(9), 1625-1631. https://doi.org/10.1016/j.cellsig.2008.05.008