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  • Original Paper
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A switch from p130Cas/Crk to Gab1/Crk signaling correlates with anchorage independent growth and JNK activation in cells transformed by the Met receptor oncoprotein

Oncogene volume 19, pages 5973–5981 (2000)Cite this article

Abstract

Cell transformation is associated with anchorage independent growth and morphological changes characterized by reduced adhesion and spreading. The molecular signals that control these events are poorly understood. The Met receptor tyrosine kinase is deregulated in human tumors and an oncogenic derivative of this receptor transforms cells. In this paper we demonstrate that fibroblasts transformed by the Met oncoprotein display decreased cell spreading consistent with the loss of actin stress fibers and vinculin staining focal adhesions. In contrast to control cells, focal adhesion kinase, p130Cas and paxillin are weakly or not detectably tyrosine phosphorylated in Met transformed cells. Moreover, although paxillin and p130Cas associate with the Crk adapter protein in control cells, they fail to associate with Crk in Met transformed cells, yet these cells are motile and capable of wound closure to the same extent as control cells. In Met transformed cells, Crk predominantly associates with the Cbl and Gab1 docking proteins in a tyrosine phosphorylation dependent manner. The coupling of Gab1, but not Cbl, with Crk is retained in cells grown in suspension and enhances JNK activation. We propose that the loss of adhesion dependent signals required for cell cycle progression is compensated through Met induced Gab1/Crk signals.

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Abbreviations

BSA:

bovine serum albumin

ERK:

extracellular regulated kinase

FAK:

focal adhesion kinase

HGF/SF:

hepatocyte growth factor/scatter factor

JNK:

c-Jun N-terminal kinase

PI3-Kinase:

phosphatidylinositol 3′-Kinase

SH2:

Src homology 2

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Acknowledgements

We thank Drs M Tremblay, N Lamarche and J Woodgett for reagents provided. The help of Minglun Wang and Dr Becky Fixman with part of the Gab1 mutagenesis is acknowledged. We thank members of the Park laboratory for their insightful comments on the manuscript. L Lamorte is a recipient of a Natural Sciences and Engineering Research Council studentship. DM Kamikura is a recipient of a Steve Fonyo National Cancer Institute of Canada studentship. M Park is a recipient of a Medical Research Council of Canada scientist award. This research was supported by an operating grant to M Park from the Medical Research Council of Canada.

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Author notes

  1. Darren M Kamikura

    Present address: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Authors and Affiliations

  1. Department of Biochemistry, Molecular Oncology Group, McGill University Hospital Center, Montreal, H3A 1A1, Quebec, Canada

    Louie Lamorte & Morag Park

  2. Department of Medicine, Molecular Oncology Group, McGill University Hospital Center, Montreal, H3A 1A1, Quebec, Canada

    Darren M Kamikura & Morag Park

  3. Department of Oncology, Molecular Oncology Group, McGill University Hospital Center, Montreal, H3A 1A1, Quebec, Canada

    Morag Park

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Lamorte, L., Kamikura, D. & Park, M. A switch from p130Cas/Crk to Gab1/Crk signaling correlates with anchorage independent growth and JNK activation in cells transformed by the Met receptor oncoprotein. Oncogene 19, 5973–5981 (2000). https://doi.org/10.1038/sj.onc.1203977

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