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  • Original Paper
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CAS promotes invasiveness of Src-transformed cells

Oncogene volume 23, pages 7406–7415 (2004)Cite this article

Abstract

CAS (‘Crk-associated substrate’) is an Src substrate found at sites of integrin-mediated cell adhesion and linked to cell motility and survival. In this study, the involvement of CAS in oncogenic transformation was evaluated through analysis of mouse embryo fibroblast populations expressing an activated Src mutant, either in the presence or absence of CAS expression. CAS was not found to be a critical determinant of either Src-mediated morphologic transformation or anchorage-independent growth. However, CAS had a profound effect on other aspects of oncogenic Src function. CAS expression led to a substantial increase in the phosphotyrosine content of FAK and paxillin, supporting a role for CAS as a positive regulator of Src activity at integrin adhesion sites. Importantly, CAS expression resulted in a striking enhancement of the capacity of Src-transformed cells to invade through Matrigel. The increased invasiveness was associated with increased activation of matrix metalloproteinase MMP-2 and formation of large actin-rich podosomal aggregates appearing as ring and belt structures. Thus, elevated CAS-associated tyrosine phosphorylation signaling events occurring at sites of integrin-mediated cell adhesion can have a major role in the development of an invasive cell phenotype.

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Acknowledgements

We thank Hisamaru Hirai and Amy Bouton for providing CAS-deficient cells and Pranathi Matta for technical assistance. This work was primarily supported by NIH/NIGMS R01 GM49882 and NIH/NIDDK R01 DK56018 (to SKH). AP was supported by NIH/NCI R01 CA94849-01 and NIH/NIDDK O'Brien Center Grant P50 DK39261-16. The work also utilized the Cell Imaging Shared Resource, the Flow Cytometry Resource Center, and the DNA Sequencing core facilities supported by the Vanderbilt Diabetes Research Training Center, the Vanderbilt Digestive Disease Research Center, and the Vanderbilt-Ingram Cancer Center.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, 37212, TN, USA

    Jan Brábek, Sábata S Constancio, Nah-Young Shin & Steven K Hanks

  2. Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, 37212, TN, USA

    Ambra Pozzi & Alissa M Weaver

  3. Department of Medicine (Nephrology), Vanderbilt University School of Medicine, Nashville, 37212, TN, USA

    Ambra Pozzi

  4. Department of Pathology, Vanderbilt University School of Medicine, Nashville, 37212, TN, USA

    Alissa M Weaver

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  1. Jan Brábek
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Correspondence to Steven K Hanks.

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Brábek, J., Constancio, S., Shin, NY. et al. CAS promotes invasiveness of Src-transformed cells. Oncogene 23, 7406–7415 (2004). https://doi.org/10.1038/sj.onc.1207965

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