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Molecular Genetics of Metastasis

  1. Georg F Weber

Published Online: 19 APR 2010

DOI: 10.1002/9780470015902.a0022447

eLS

eLS

How to Cite

Weber, G. F. 2010. Molecular Genetics of Metastasis. eLS. .

Author Information

  1. University of Cincinnati, Cincinnati, Ohio, USA

Publication History

  1. Published Online: 19 APR 2010

Abstract

Metastasis is the spread of cancer cells throughout the body. Although it is frequently the cause of death from malignant growths, it is the most poorly understood aspect of carcinogenesis. The underlying process of cancer cell dissemination is controlled by genetic programs in the tumour cells and in the host. The tumour cell-intrinsic genetic programs of metastasis confer invasiveness and anchorage-independence. The responsible genes are typically deregulated by aberrant expression or splicing. Organ preference of metastasis depends on more complex tumour–host interactions. Metastasis suppressor genes, when expressed, can negatively regulate tumour spread. The molecular genetics of metastasis has led to the development of diagnostic tests, based on gene expression profiles that help predict metastatic potential. Further, it has opened prospects for the targeting of key culprit genes in antimetastasis therapy.

Key Concepts:

  • Cancer invasiveness constitutes the breaking of tumour cells through tissue barriers and represents the earliest manifestation of metastasis.

  • The genetic basis of metastasis formation is the aberrant expression or splicing of stress response genes.

  • The biologic activity of metastasis-mediating gene products is extensively regulated by posttranscriptional mechanisms.

  • Cancer metastasis is guided by two intrinsic characteristics of cancer cells, invasiveness and anchorage-independent survival.

  • Cancer cell invasiveness is mediated by secreted proteases, homing receptors, cytokine ligands and associated signalling molecules.

  • The acquisition of invasiveness by tumour cells is accompanied by a characteristic, reversible remodelling, called the epithelial-mesenchymal transition.

  • Cancers shed their tumour cells into the blood or lymph stream from the earliest stages of growth on; most cells die in the circulation.

  • Fully transformed cells can survive without anchorage for extended periods of time.

  • Genetic programs of metastasis encode consistent patterns of organ preference by individual malignancies.

  • Like other functions within cancer cells, the ability to metastasise is under positive and negative genetic control.

Keywords:

  • metastasis;
  • invasion;
  • anoikis;
  • homing receptor;
  • cytokine;
  • protease