Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness.
Tumour cell invasiveness is crucial for cancer metastasis and is not yet understood. Here we describe two functional screens for proteins required for the invasion of fibrosarcoma cells that identified the molecular chaperone heat shock protein 90 (hsp90). The hsp90 alpha isoform, but not hsp90 beta, is expressed extracellularly where ... it interacts with the matrix metalloproteinase 2 (MMP2). Inhibition of extracellular hsp90 alpha decreases both MMP2 activity and invasiveness. This role for extracellular hsp90 alpha in MMP2 activation indicates that cell-impermeant anti-hsp90 drugs might decrease invasiveness without the concerns inherent in inhibiting intracellular hsp90.
Mesh Terms:
Basement Membrane, Binding Sites, Cell Line, Tumor, Cell Membrane, Enzyme Inhibitors, Extracellular Matrix, Fibrosarcoma, HSP90 Heat-Shock Proteins, Humans, Matrix Metalloproteinase 2, Neoplasm Invasiveness, Protein Binding, Protein Interaction Mapping, Protein Isoforms, Protein Structure, Tertiary, Proteomics
Basement Membrane, Binding Sites, Cell Line, Tumor, Cell Membrane, Enzyme Inhibitors, Extracellular Matrix, Fibrosarcoma, HSP90 Heat-Shock Proteins, Humans, Matrix Metalloproteinase 2, Neoplasm Invasiveness, Protein Binding, Protein Interaction Mapping, Protein Isoforms, Protein Structure, Tertiary, Proteomics
Nat. Cell Biol.
Date: Jun. 01, 2004
PubMed ID: 15146192
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