Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development

Lidiya S. Orlichenko, Derek C Radisky

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) are a family of more than 28 enzymes that were initially identified on the basis of their ability to cleave most elements of the extracellular matrix (ECM) but have subsequently been found to be upregulated in nearly every tumor type. As digestion of the ECM is essential for tumor invasion and metastasis, MMPs have been studied for their role in these later stages of tumor development. More recently, exposure to these enzymes has been found to impact cellular signaling pathways that stimulate cell growth at early stages of tumor progression. MMPs have also been found to cleave intracellular targets and so inducing mitotic abnormalities and genomic instability. Emerging evidence indicates that tumor-associated MMPs can also stimulate processes associated with epithelial-mesenchymal transition (EMT), a developmental process that is activated in tumor cells during cell invasion and metastasis. Investigations of potential therapeutic MMP inhibitors aimed at blocking the protumorigenic tissue alterations induced by MMPs have been complicated by the side effects associated with nonspecific inhibition of normal physiological processes; recent investigations have shown how delineation of the extracellular targets and intracellular signaling pathways by which MMP action on cancer cells can induce EMT provides insight into novel therapeutic targets. Here, we provide an overview of recent findings of MMP action in tumors and the mechanisms by which MMPs induce both phenotypic and genotypic alterations that facilitate tumor progression.

Original languageEnglish (US)
Pages (from-to)593-600
Number of pages8
JournalClinical and Experimental Metastasis
Volume25
Issue number6
DOIs
StatePublished - Oct 2008

Fingerprint

Epithelial-Mesenchymal Transition
Matrix Metalloproteinases
Neoplasms
Extracellular Matrix
Physiological Phenomena
Neoplasm Metastasis
Matrix Metalloproteinase Inhibitors
Genomic Instability
Enzymes
Digestion

Keywords

  • Cancer
  • Epithelial-mesenchymal transition
  • Invasion
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Cancer Research

Cite this

Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development. / Orlichenko, Lidiya S.; Radisky, Derek C.

In: Clinical and Experimental Metastasis, Vol. 25, No. 6, 10.2008, p. 593-600.

Research output: Contribution to journalArticle

@article{412a186075574a0d8853683807601003,
title = "Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development",
abstract = "Matrix metalloproteinases (MMPs) are a family of more than 28 enzymes that were initially identified on the basis of their ability to cleave most elements of the extracellular matrix (ECM) but have subsequently been found to be upregulated in nearly every tumor type. As digestion of the ECM is essential for tumor invasion and metastasis, MMPs have been studied for their role in these later stages of tumor development. More recently, exposure to these enzymes has been found to impact cellular signaling pathways that stimulate cell growth at early stages of tumor progression. MMPs have also been found to cleave intracellular targets and so inducing mitotic abnormalities and genomic instability. Emerging evidence indicates that tumor-associated MMPs can also stimulate processes associated with epithelial-mesenchymal transition (EMT), a developmental process that is activated in tumor cells during cell invasion and metastasis. Investigations of potential therapeutic MMP inhibitors aimed at blocking the protumorigenic tissue alterations induced by MMPs have been complicated by the side effects associated with nonspecific inhibition of normal physiological processes; recent investigations have shown how delineation of the extracellular targets and intracellular signaling pathways by which MMP action on cancer cells can induce EMT provides insight into novel therapeutic targets. Here, we provide an overview of recent findings of MMP action in tumors and the mechanisms by which MMPs induce both phenotypic and genotypic alterations that facilitate tumor progression.",
keywords = "Cancer, Epithelial-mesenchymal transition, Invasion, Matrix metalloproteinases",
author = "Orlichenko, {Lidiya S.} and Radisky, {Derek C}",
year = "2008",
month = "10",
doi = "10.1007/s10585-008-9143-9",
language = "English (US)",
volume = "25",
pages = "593--600",
journal = "Clinical and Experimental Metastasis",
issn = "0262-0898",
publisher = "Springer Netherlands",
number = "6",

}

TY - JOUR

T1 - Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development

AU - Orlichenko, Lidiya S.

AU - Radisky, Derek C

PY - 2008/10

Y1 - 2008/10

N2 - Matrix metalloproteinases (MMPs) are a family of more than 28 enzymes that were initially identified on the basis of their ability to cleave most elements of the extracellular matrix (ECM) but have subsequently been found to be upregulated in nearly every tumor type. As digestion of the ECM is essential for tumor invasion and metastasis, MMPs have been studied for their role in these later stages of tumor development. More recently, exposure to these enzymes has been found to impact cellular signaling pathways that stimulate cell growth at early stages of tumor progression. MMPs have also been found to cleave intracellular targets and so inducing mitotic abnormalities and genomic instability. Emerging evidence indicates that tumor-associated MMPs can also stimulate processes associated with epithelial-mesenchymal transition (EMT), a developmental process that is activated in tumor cells during cell invasion and metastasis. Investigations of potential therapeutic MMP inhibitors aimed at blocking the protumorigenic tissue alterations induced by MMPs have been complicated by the side effects associated with nonspecific inhibition of normal physiological processes; recent investigations have shown how delineation of the extracellular targets and intracellular signaling pathways by which MMP action on cancer cells can induce EMT provides insight into novel therapeutic targets. Here, we provide an overview of recent findings of MMP action in tumors and the mechanisms by which MMPs induce both phenotypic and genotypic alterations that facilitate tumor progression.

AB - Matrix metalloproteinases (MMPs) are a family of more than 28 enzymes that were initially identified on the basis of their ability to cleave most elements of the extracellular matrix (ECM) but have subsequently been found to be upregulated in nearly every tumor type. As digestion of the ECM is essential for tumor invasion and metastasis, MMPs have been studied for their role in these later stages of tumor development. More recently, exposure to these enzymes has been found to impact cellular signaling pathways that stimulate cell growth at early stages of tumor progression. MMPs have also been found to cleave intracellular targets and so inducing mitotic abnormalities and genomic instability. Emerging evidence indicates that tumor-associated MMPs can also stimulate processes associated with epithelial-mesenchymal transition (EMT), a developmental process that is activated in tumor cells during cell invasion and metastasis. Investigations of potential therapeutic MMP inhibitors aimed at blocking the protumorigenic tissue alterations induced by MMPs have been complicated by the side effects associated with nonspecific inhibition of normal physiological processes; recent investigations have shown how delineation of the extracellular targets and intracellular signaling pathways by which MMP action on cancer cells can induce EMT provides insight into novel therapeutic targets. Here, we provide an overview of recent findings of MMP action in tumors and the mechanisms by which MMPs induce both phenotypic and genotypic alterations that facilitate tumor progression.

KW - Cancer

KW - Epithelial-mesenchymal transition

KW - Invasion

KW - Matrix metalloproteinases

UR - http://www.scopus.com/inward/record.url?scp=47549089080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47549089080&partnerID=8YFLogxK

U2 - 10.1007/s10585-008-9143-9

DO - 10.1007/s10585-008-9143-9

M3 - Article

VL - 25

SP - 593

EP - 600

JO - Clinical and Experimental Metastasis

JF - Clinical and Experimental Metastasis

SN - 0262-0898

IS - 6

ER -