Cell Biology

Prepare for Invasion

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Science  04 Jun 2004:
Vol. 304, Issue 5676, pp. 1417
DOI: 10.1126/science.304.5676.1417b

An important factor in the relative seriousness of cancer is the invasiveness of the constituent tumor cells causing metastasis. Eustace et al. used two independent in vitro proteomic screens on fibrosarcoma cells in an attempt to define cell surface proteins involved in cellular invasiveness. In both screens, a molecular chaperone protein isoform, HSP90α, was found to be involved. HSP90α was expressed on the surface of invasive cells, where it interacted with matrix metalloproteinase 2 (MMP2), the protease implicated in digesting the extracellular matrix during tumor invasion. By inhibiting extracellular HSP90α, the activity of MMP2 was reduced and so was cellular invasiveness. Both fibrosarcoma and breast cancer cells express HSP90α on the cell surface. The authors suggest that impermeant inhibitors of HSP90α might be able to inhibit tumor invasiveness without affecting the important intracellular functions of other HSP90 isoforms. — SMH

Nature Cell Biol. 10.1038/ncb1131 (2004)

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