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Dissecting Oncogenic RTK Pathways in Colorectal Cancer Initiation and Progression

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Colorectal Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1765))

Abstract

Colorectal cancer (CRC) is a progressive disorder associated with an accumulation of multiple heterogeneous genetic alterations in intestinal epithelial cells (IEC). However, when these cells undergo neoplastic transformation and become cancerous and metastatic, they invariably acquire hallmarks conferring them the ability to hyperproliferate, escape growth-inhibitory and death-inducing cues, and promote angiogenesis as well as epithelial-to-mesenchymal transformation (EMT), fostering their invasive dissemination from primary tumor into distant tissues. Compelling clinical and experimental evidence suggest that aberrant engagement of cell surface growth factor receptor tyrosine kinase (RTK) signaling, like that of the hepatocyte growth factor (HGF)/MET receptor, underlies CRC metastatic progression by promoting these cancer hallmarks. To date, though, the use of RTK-targeting agents has been viewed as a promising approach for the treatment of metastatic CRC, clinical success has been modest.

Our vision is that the prospect of designing RTK-based, improved and innovative CRC therapies and prognostic markers likely rests on a comprehensive understanding of the biological processes and underlying regulatory molecular mechanisms by which deregulation of RTK signaling governs IEC’s neoplastic transformation and their transition from noninvasive to metastatic and malignant cells. Herein, we describe our scheme for defining the full scope of oncogenic MET-driven cancer biological processes, in cellulo and in vivo, as well as the individual contribution of MET-binding effectors in a nontransformed IEC model, the IEC-6 cell line.

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Acknowledgments

This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR, MOP-106476) awarded to CS.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, QC, Canada

    Stephen McManus, Walid Chababi & Caroline Saucier

  2. Department of Pediatrics, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, QC, Canada

    Dominique Arsenault & Claire M. Dubois

  3. Department of Immunology Division, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, QC, Canada

    Dominique Arsenault & Claire M. Dubois

Authors
  1. Stephen McManus
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  2. Walid Chababi
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  3. Dominique Arsenault
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  4. Claire M. Dubois
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  5. Caroline Saucier
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Corresponding author

Correspondence to Caroline Saucier .

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Editors and Affiliations

  1. Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Science, Université de Sherbrooke, Sherbrooke, Québec, Canada

    Jean-François Beaulieu

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McManus, S., Chababi, W., Arsenault, D., Dubois, C.M., Saucier, C. (2018). Dissecting Oncogenic RTK Pathways in Colorectal Cancer Initiation and Progression. In: Beaulieu, JF. (eds) Colorectal Cancer. Methods in Molecular Biology, vol 1765. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7765-9_2

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  • DOI: https://doi.org/10.1007/978-1-4939-7765-9_2

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7764-2

  • Online ISBN: 978-1-4939-7765-9

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