Dynamic matrisome

ECM remodeling factors licensing cancer progression and metastasis

Arseniy E. Yuzhalin*, Su Yin Lim, Anton G. Kutikhin, Alex N. Gordon-Weeks

*Corresponding author for this work

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

The main cause of cancer-related mortality, metastasis, is a complex, multi-step process. The extracellular matrix (ECM) component of solid tumors has been implicated in metastatic progression; however, the ECM exists as a complex macromolecular substrate and it is unclear how its molecular composition promotes cancer progression. ECM homeostasis is regulated by various secreted proteins including cross-linkers (e.g., lysyl oxidases and transglutaminases), modifying enzymes (e.g., sulfatases and extracellular kinases), proteases (e.g., matrix metalloproteinases, heparanase, and cathepsins) and protease inhibitors (e.g., tissue inhibitors of metalloproteinases, cystatins, and serpins); each of which can alter the structural, mechanical, and biochemical properties of the ECM. Emerging evidence indicates that altered ECM regulator activity in cancer triggers pathological ECM remodeling facilitating metastatic dissemination making ECM regulators potential targets for cancer therapy. In this review, we summarize and critically discuss the existing literature on the role of ECM regulators in cancer metastasis.

Original languageEnglish
Pages (from-to)207-228
Number of pages22
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1870
Issue number2
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Cancer
  • Cathepsins
  • Cystatins
  • Extracellular matrix
  • Lysyl oxidases
  • Matrix metalloproteinases
  • Metastasis
  • Tissue inhibitors of metalloproteinases

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