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Differential activation of ERKs to focal adhesions by PKC ε is required for PMA-induced adhesion and migration of human glioma cells

Oncogene volume 20, pages 7398–7407 (2001)Cite this article

Abstract

Protein kinase C (PKC) is a family of serine/threonine kinases involved in the transduction of a variety of signals. There is increasing evidence to indicate that specific PKC isoforms are involved in the regulation of distinct cellular processes. In glioma cells, PKC α was found to be a critical regulator of proliferation and cell cycle progression, while PKC ε was found to regulate adhesion and migration. Herein, we report that specific PKC isoforms are able to differentially activate extracellular-signal regulated kinase (ERK) in distinct cellular locations: while PKC α induces the activation of nuclear ERK, PKC ε induces the activation of ERK at focal adhesions. Inhibition of the ERK pathway completely abolished the PKC-induced integrin-mediated adhesion and migration. Thus, we present the first evidence that PKC ε is able to activate ERK at focal adhesions to mediate glioma cell adhesion and motility, providing a molecular mechanism to explain the different biological functions of PKC α and ε in glioma cells.

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References

  • Besson A, Yong VW . 2000 Mol. Cell. Biol. 20: 4580–4590

  • Berens ME, Giese A . 1999 Neoplasia 1: 208–219

    Article  CAS  Google Scholar 

  • El-Obeid A, Bongcam-Rudloff E, Sorby M, Ostman A, Nister M, Westermark B . 1997 Cancer Res. 57: 5598–5604

  • El-Shemerly MYM, Besser D, Nagasawa M, Nagamine Y . 1997 J. Biol. Chem. 272: 30599–30602

    Article  CAS  Google Scholar 

  • Fincham VJ, James M, Frame MC, Winder SJ . 2000 EMBO J. 19: 2911–2923

  • Friedlander DR, Zagzag D, Shiff B, Cohen H, Allen JC, Kelly PJ, Grumet M . 1996 Cancer Res. 56: 1939–1947

  • Garrington TP, Johnson GL . 1999 Curr. Opin. Cell Biol. 11: 211–218

  • Giancotti FG, Ruoslahti E . 1999 Science 285: 1028–1032

    Article  CAS  Google Scholar 

  • Gillespie GY, Soroceanu L, Manning TJ, Gladson CL, Rosenfeld SS . 1999 Cancer Res. 59: 2076–2082

  • Holland EC . 2000 Proc. Natl. Acad. Sci. USA 97: 6242–6244

  • Howe AK, Juliano RL . 1998 J. Biol. Chem. 273: 27268–27274

    Article  CAS  Google Scholar 

  • Khoshyomm S, Penar PL, Rossi J, Wells A, Abramson DL, Bhushan A . 1999 Neurosurgery 44: 568–578

    Article  CAS  Google Scholar 

  • Klemke RL, Cai S, Giannini AL, Gallagher PJ, De Lanerolle P, Cheresch DA . 1997 J. Cell Biol. 137: 481–492

  • Klinghoffer RA, Sachsenmaier C, Cooper JA, Soriano P . 1999 EMBO J. 18: 2459–2471

    Article  CAS  Google Scholar 

  • Lund-Johansen M, Bjerkvig R, Humphrey PA, Bigner SH, Bigner DD, Laerum OD . 1990 Cancer Res. 50: 6039–6044

  • Miranti CK, Ohno S, Brugge JS . 1999 J. Biol. Chem. 274: 10571–10581

    Article  CAS  Google Scholar 

  • Newton AC . 1997 Curr. Opin. Cell Biol. 9: 161–167

  • Nguyen DHD, Catling AD, Webb DJ, Sankovic M, Walker LA, Somlyo AV, Weber MK, Gonias SL . 1999 J. Cell. Biol. 146: 149–164

  • Rigot V, Lehmann M, Andre F, Daemi N, Marvaldi J, Luis J . 1998 J. Cell Sci. 111: 3119–3127

  • Schaeffer HJ, Weber MJ . 1999 Mol. Cell. Biol. 19: 2435–2444

    Article  CAS  Google Scholar 

  • Schonwasser DC, Marais RM, Marshall CJ, Parker PJ . 1998 Mol. Cell. Biol. 18: 790–798

    Article  Google Scholar 

  • Short SM, Boyer JL, Juliano RL . 2000 J. Biol. Chem. 275: 12970–12977

    Article  CAS  Google Scholar 

  • Sieg DJ, Hauck CR, Schlaepfer DD . 1999 J. Cell Sci. 112: 2677–2691

  • Traub O, Monia BP, Dean NM, Berk BC . 1997 J. Biol. Chem. 272: 31251–31257

    Article  CAS  Google Scholar 

  • Tysnes OB, Laerum OD . 1993 Anticancer Res. 13: 1325–1330

  • Zhang W, Law RE, Hinton DR, Couldwell WT . 1997 Cancer Lett. 120: 31–38

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Acknowledgements

We gratefully thank Tammy L Wilson for technical assistance in the adhesion assays. This work is supported by a grant from the Canadian Institutes for Health Research. A Besson is a Research Student of the National Cancer Institute of Canada supported with funds provided by the Terry Fox Run. A Davy is the recipient of an Alberta Cancer Board postdoctoral fellowship. SM Robbins is a scholar of the Alberta Heritage Foundation for Medical Research and holds a Canada Research Chair in Cancer Biology. VW Yong is a Medical Research Council of Canada Scientist and a senior scholar of the Alberta Heritage Foundation for Medical Research.

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Authors and Affiliations

  1. Department of Oncology, University of Calgary, Calgary, T2N 4N1, Alberta, Canada

    Arnaud Besson, Alice Davy, Stephen M Robbins & V Wee Yong

  2. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, T2N 4N1, Alberta, Canada

    Alice Davy & Stephen M Robbins

  3. Department of Clinical Neurosciences, University of Calgary, Calgary, T2N 4N1, Alberta, Canada

    V Wee Yong

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  1. Arnaud Besson
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  2. Alice Davy
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Correspondence to V Wee Yong.

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Besson, A., Davy, A., Robbins, S. et al. Differential activation of ERKs to focal adhesions by PKC ε is required for PMA-induced adhesion and migration of human glioma cells. Oncogene 20, 7398–7407 (2001). https://doi.org/10.1038/sj.onc.1204899

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