Regulation of matrix metalloproteinase expression in tumor invasion.
Degradation of basement membranes and stromal extracellular matrix (ECM) is crucial for invasion and metastasis of malignant cells. Degradation of ECM is initiated by proteinases secreted by different cell types participating in tumor cell invasion, and increased expression or activity of every known class of proteinases (metallo-, serine-, aspartic-, and cysteine) has been linked to malignancy and invasion of tumor cells. Studies performed over the last decade have revealed that matrix metalloproteinases (MMPs) play a crucial role in tumor invasion. Expression of MMP genes is transcriptionally regulated by a variety of extracellular factors including cytokines, growth factors, and cell contact to ECM. This review will summarize the current view on the role of MMPs in tumor growth, invasion, and survival, and focus on the role of mitogen-activated protein kinases and AP-1 and ETS transcription factors in the regulation of MMP gene expression during invasion process.
Westermarck
J
J
MediCity Research Laboratory, Department of Medical Biochemistry, University of Turku, Finland. jukwes@utu.fi
Kähäri
V M
VM
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000503:physiopathology*; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D018808:Transcription Factor AP-1; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D008666:Metalloendopeptidases