Delineating protease functions during cancer development

Nesrine I. Affara, Pauline Andreu, Lisa Coussens

Research output: Chapter in Book/Report/Conference proceedingChapter

39 Citations (Scopus)

Abstract

Much progress has been made in understanding how matrix remodeling proteases, including metalloproteinases, serine proteases, and cysteine cathepsins, functionally contribute to cancer development. In addition to modulating extracellular matrix metabolism, proteases provide a significant protumor advantage to developing neoplasms through their ability to modulate bioavailability of growth and proangiogenic factors, regulation of bioactive chemokines and cytokines, and processing of cell-cell and cell-matrix adhesion molecules. Although some proteases directly regulate these events, it is now evident that some proteases indirectly contribute to cancer development by regulating posttranslational activation of latent zymogens that then directly impart regulatory information. Thus, many proteases act in a cascade-like manner and exert their functionality as part of a proteolytic pathway rather than simply functioning individually. Delineating the cascade of enzymatic activities contributing to overall proteolysis during carcinogenesis may identify rate-limiting steps or pathways that can be targeted with anti-cancer therapeutics. This chapter highlights recent insights into the complexity of roles played by pericellular and intracellular proteases by examining mechanistic studies as well as the roles of individual protease gene functions in various organ-specific mouse models of cancer development, with an emphasis on intersecting proteolytic activities that amplify programming of tissues to foster neoplastic development.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
Pages1-32
Number of pages32
Volume539
DOIs
StatePublished - 2009
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume539
ISSN (Print)10643745

Fingerprint

Peptide Hydrolases
Neoplasms
Cell-Matrix Junctions
Cathepsins
Enzyme Precursors
Cell Adhesion Molecules
Metalloproteases
Serine Proteases
Chemokines
Biological Availability
Proteolysis
Extracellular Matrix
Cysteine
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Cytokines
Genes

Keywords

  • ADAMs
  • Angiogenesis
  • Cancer
  • Cysteine cathepsins
  • ECM remodeling
  • Inflammation
  • Metalloproteinases
  • Mouse models
  • Plasminogen activators
  • Proteases
  • Proteolytic cascades
  • Serine proteases

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Affara, N. I., Andreu, P., & Coussens, L. (2009). Delineating protease functions during cancer development. In Methods in Molecular Biology (Vol. 539, pp. 1-32). (Methods in Molecular Biology; Vol. 539). https://doi.org/10.1007/978-1-60327-003-8_1

Delineating protease functions during cancer development. / Affara, Nesrine I.; Andreu, Pauline; Coussens, Lisa.

Methods in Molecular Biology. Vol. 539 2009. p. 1-32 (Methods in Molecular Biology; Vol. 539).

Research output: Chapter in Book/Report/Conference proceedingChapter

Affara, NI, Andreu, P & Coussens, L 2009, Delineating protease functions during cancer development. in Methods in Molecular Biology. vol. 539, Methods in Molecular Biology, vol. 539, pp. 1-32. https://doi.org/10.1007/978-1-60327-003-8_1
Affara NI, Andreu P, Coussens L. Delineating protease functions during cancer development. In Methods in Molecular Biology. Vol. 539. 2009. p. 1-32. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-60327-003-8_1
Affara, Nesrine I. ; Andreu, Pauline ; Coussens, Lisa. / Delineating protease functions during cancer development. Methods in Molecular Biology. Vol. 539 2009. pp. 1-32 (Methods in Molecular Biology).
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