AI Article Synopsis
- Tumour cell invasiveness is vital for cancer spreading, but the underlying mechanisms are not fully understood.
- The study identifies the heat shock protein 90 (hsp90), specifically its alpha isoform, as a key player in the invasion of fibrosarcoma cells by interacting with the matrix metalloproteinase 2 (MMP2).
- Targeting extracellular hsp90 alpha with anti-hsp90 drugs could potentially reduce cancer cell invasiveness without affecting intracellular functions, offering a safer therapeutic approach.
Article Abstract
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.
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