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Epithelial Cell Signalling in Colorectal Cancer Metastasis

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Metastasis of Colorectal Cancer

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 14))

Abstract

The development of metastatic tumours is a complex process that consists of a series of cellular events that shift neoplastic cells from the primary tumour to a distant location (Chambers et al., 2002). Cancer cells must first detach from the primary tumour and invade the surrounding stroma, degrade the basement membrane, disseminate and survive into the circulatory systems, and ultimately extravasate and colonize a new microenvironment. Research of the past decades has revealed that complex and redundant signalling pathways in both tumour and the microenvironment govern tumour cell invasion at the primary site, survival in the bloodstream, and progressive outgrowth at distant sites. In this chapter, we highlight the role of growth factor receptor tyrosine kinase (RTK) signalling pathways in progression of colorectal cancer (CRC) to advanced metastatic disease, with a particular focus on those leading to activation of the proliferative RAS/Mitogen-activated protein kinase (MAPK) and survival Phosphatidylinositol 3-kinase (PI3K)/AKT pathways in epithelial colorectal cancer cells.

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Abbreviations

ACF:

Aberrant crypt foci

Bcl-2:

B-cell lymphoma protein 2

Bcl-xL :

B-cell lymphoma extra-large protein

BM:

Basal membrane

Cbl:

Casitas B-cell lymphoma protein

CEA:

Carcinoembryonic antigen

CRC:

Colorectal cancer

COX:

Cyclooxygenase

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

Gab1:

Grb2-associated binding protein-1

Grb2:

Growth factor receptor-bound protein 2

HGF:

Hepatocyte growth factor

HIF-1:

Hypoxia-inducible factor-1

IGFR:

Insulin-like growth factor

MACC1:

Metastasis-associated in colon cancer 1

MAPK:

Mitogen-activated protein kinase

Mcl-1:

Myeloid leukemia cell differentiation protein

MMP2:

Metalloproteinase 2

NF-κB:

Nuclear factor kappa light chain in activated B cells

NSAIDs:

Non-steroidal anti-inflammatory drugs

PDGFR:

Platelet-derived growth factor

PIP3:

Phosphatidylinositol 3,4,5-triphosphate

PI3K:

Phosphatidyl inositol 3-kinase

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

PRL-3:

Phosphatase of regenerating liver 3

RTK:

Receptor tyrosine kinase

PTB:

Phosphotyrosine binding domain

RAS-GAP:

RAS-GTPase activating protein

Shc:

Src-homology collagen protein

SH2:

Src homology domain 2

SOS:

Son of Sevenless

TGF:

Transforming growth factor

TSP:

Thrombospondin

uPA:

Urokinase plasminogen activator

uPAR:

uPA receptor

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgments

We are thankful to members of our laboratories for their research work and helpful discussions. We are particularly grateful to Véronique Pomerleau and Sébastien Cagnol for their critical reading of the chapter. We apologize to the authors whose work was not cited because of space limitation. Our cancer research program is supported by grants from the Canadian Institutes of Health (C.S., MOP-84382; N.R., MOP-14405) and the Cancer Research Society (to N.R.). The authors are members of the FRSQ-funded Centre de Recherche Clinique Étienne LeBel and of the CIHR team on the Digestive Epithelium. C.S. is a scholar from the Fonds de la Recherche en Santé du Québec and N.R. is a recipient of a Canadian Research Chair in Signalling and Digestive Physiopathology.

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  1. Département d’Anatomie et de Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada

    Caroline Saucier & Nathalie Rivard

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  1. Caroline Saucier
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  2. Nathalie Rivard
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Correspondence to Caroline Saucier .

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  1. Rosalind & Morris Goodman Cancer, Research Centre, McGill University, Promenade Sir William Osler 3655, Montreal, H3G 1Y6, Canada

    Nicole Beauchemin

  2. Hôpital L’Hôtel-Dieu de Québec, Centre de Recherche en Cancérologie, Université Laval, rue McMahon 9, Quebec, G1R 2J6, Canada

    Jacques Huot

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Saucier, C., Rivard, N. (2010). Epithelial Cell Signalling in Colorectal Cancer Metastasis. In: Beauchemin, N., Huot, J. (eds) Metastasis of Colorectal Cancer. Cancer Metastasis - Biology and Treatment, vol 14. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8833-8_8

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