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Role of Integrins in Regulating Proteases to Mediate Extracellular Matrix Remodeling

  • Original Paper
  • Published:
Cancer Microenvironment

Abstract

The extracellular matrix (ECM) is an extracellular scaffold composed of complex mixtures of proteins that plays a pivotal role in tumor progression. ECM remodeling is crucial for tumor migration and invasion during the process of metastasis. ECM can be remodeled by several processes including synthesis, contraction and proteolytic degradation. In order to cross through the ECM barriers, malignant cells produce a spectrum of extracellular proteinases including matrix metalloproteinases (MMPs), serine proteases (mainly the urokinase plasminogen activator (uPA) system) and cysteine proteases to degrade ECM components. As major adhesion molecules to support cell attachment to ECM, integrins play critical roles in tumor progression by enhancing tumor cell survival, migration and invasion. Previous studies have shown that integrins can regulate the expression and activity of these proteases through different pathways. This review summarizes the roles of MMPs and uPA system in ECM remodeling and discusses the regulatory functions of integrins on these proteases in invasive tumors.

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Abbreviations

ECM:

Extracellular matrix

MMP:

Matrix metalloproteinase

uPA:

Urokinase plasminogen activator

CAM:

Cell adhesion molecule

ILK:

Integrin-linked kinase

FAK:

Focal adhesion kinase

MT-MMP:

Membrane-anchored type matrix metalloproteinase

TIMP:

Tissue inhibitor of metalloproteinase

RECK:

Reversion-inducing cysteine-rich protein with kazal motifs

SCC:

Squamous cell carcinoma

HMW:

High molecular weight

JNK:

c-Jun N-terminal kinase

uPAR:

uPA receptor

PAI:

Plasminogen activator inhibitor

MPI:

MMP inhibitor

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Acknowledgements

This work was supported by grants from the National Basic Research Program of China (2010CB529703), National Natural Science Foundation of China (31190061, 30700119, 30970604), Science and Technology Commission of Shanghai Municipality (11JC1414200) and the Shanghai Pujiang Program (08PJ1410600).

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  1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 YueYang Road, Shanghai, 200031, China

    Jiao Yue, Kun Zhang & JianFeng Chen

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  1. Jiao Yue
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Correspondence to JianFeng Chen.

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Yue, J., Zhang, K. & Chen, J. Role of Integrins in Regulating Proteases to Mediate Extracellular Matrix Remodeling. Cancer Microenvironment 5, 275–283 (2012). https://doi.org/10.1007/s12307-012-0101-3

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