EGFR signaling in invasion, angiogenesis and metastasis

  • Carol Box
  • Joanna Peak
  • Susanne Rogers
  • Suzanne Eccles
Chapter
First Online:
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Tumor invasion and metastasis are the hallmarks of advanced stage cancer and are associated with poor patient prognosis. EGFR is overexpressed in a variety of tumor types and this frequently correlates with a more aggressive tumor phenotype. In this chapter, we discuss the cellular and molecular mechanisms by which EGFR contributes to tumor progression and present evidence from experimental and clinical observations that reinforce the notion that EGFR actively contributes to the onset of metastatic disease. EGFR plays a key role in the regulation of processes central to tumor invasion including cell adhesion and motility through its interactions with molecules such as integrins, cadherins, phospholipase Cγ1 and phosphoinositide 3-kinase. In addition, EGFR signaling can contribute to both proteolysis and angiogenesis through up-regulated expression of matrix metalloproteinases (MMPs) and angiogenic cytokines e.g. VEGF-A and IL-8. The significance of these contributions to tumor invasion and metastasis is highlighted by the fact that a mutant, constitutively active receptor (EGFRvIII) associated with human cancers can induce these behaviors when transfected into fibroblasts. Finally, we discuss the use of EGFR antagonists to stem metastatic disease and their potential, in combination with additional novel agents, to improve treatment for cancer patients.

Keywords

invasion adhesion motility proteolysis angiogenesis lymphangiogenesis metastasis 
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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Carol Box
    • 1
  • Joanna Peak
    • 1
  • Susanne Rogers
    • 2
  • Suzanne Eccles
    • 3
  1. 1.Tumour Biology and Metastasis Team, CR-UK Centre For Cancer TherapeuticsMcElwain Laboratories, Institute of Cancer ResearchSuttonUK
  2. 2.Head and Neck UnitRoyal Marsden HospitalLondonUK
  3. 3.McElwain LaboratoriesInstitute of Cancer ResearchSuttonUK

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