Impact of proteolytic enzymes in colorectal cancer development and progression

World J Gastroenterol. 2014 Oct 7;20(37):13246-57. doi: 10.3748/wjg.v20.i37.13246.


Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.

Keywords: Adenoma; Biomarker; Cathepsin; Colorectal cancer; Invasion; Matrix metalloproteinase; Metastasis; Plasminogen activator; Prognosis; Proteinase.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Basement Membrane / metabolism
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Drug Design
  • Extracellular Matrix / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / therapeutic use


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protease Inhibitors
  • Peptide Hydrolases