Abstract
Hepatocyte growth factor (HGF) markedly induced the spreading, dissociation and scattering of Madin–Darby canine kidney epithelial cells (MDCK) and human stomach adenocarcinoma cells (TMK1). Scattering of MDCK and TMK1 cells was induced by 12-O-tetradecanoyl-phorbol-13-acetate (PMA) and epidermal growth factor (EGF), respectively. In all these agent-stimulated cells, rapid activation of Raf-1, MAP kinase/ERK kinase (MEK), 41/43 kDa MAP kinases and p90rsk was commonly observed. In contrast, PMA neither induced the scattering nor activation of all these kinases in TMK1 cells. Pretreatment of MDCK and TMK1 cells with 2-(2-amino-3-methoxyphenyl) choromone (AMPC), a specific inhibitor of MEK, selectively inhibited the HGF-, PMA- and EGF-stimulated activities of MEK, 41/43 kDa MAP kinases and p90rsk in a dose dependent manner. AMPC-pretreatment, however, did not affect HGF-, PMA- or EGF-induced activation of Raf-1, nor HGF-induced activation of phosphatidylinositol 3-kinase in these cells. Importantly, HGF-, PMA- and EGF-induced scattering of MDCK and TMK1 cells was inhibited at doses of AMPC similar to those that gave comparable levels of inhibition of the activities of MEK, 41/43 kDa MAP kinases and p90rsk. These results suggest that activation of the 41/43 kDa MAP kinase signaling pathway is required for the motility response of MDCK and TMK1 cells induced by agents such as HGF, PMA and EGF.
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tanimura, S., Chatani, Y., Hoshino, R. et al. Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering. Oncogene 17, 57–65 (1998). https://doi.org/10.1038/sj.onc.1201905
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201905
- Springer Nature Limited
Keywords
This article is cited by
-
CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy
Tumor Biology (2016)
-
Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts
Journal of Translational Medicine (2015)
-
Coordinated integrin and growth factor regulation of primary keratinocyte migration mediated through extracellular signal regulated kinase and phosphoinositide 3-kinase
Archives of Dermatological Research (2009)
-
Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail
The EMBO Journal (2006)
-
Increase in hepatocyte growth factor receptor tyrosine kinase activity in renal carcinoma cells is associated with increased motility partly through phosphoinositide 3-kinase activation
Oncogene (2001)