Abstract
HSP90 is released by cancer cells in the tumor microenvironment where it associates with different co-chaperones generating complexes with specific functions, ranging from folding and activation of extracellular clients to the stimulation of cell surface receptors. Emerging data indicate that these functions are essential for tumor growth and progression. The understanding of the exact composition of extracellular HSP90 complexes and the molecular mechanisms at the basis of their functions in the tumor microenvironment may represent the first step to design innovative diagnostic tools and new effective therapies. Here we review the impact of extracellular HSP90 complexes on cancer cell signaling and behavior.
Highlights
In order to survive and proliferate in a highly stressful environment cancer cells upregulate chaperone expression and actively release chaperones in the extracellular milieu to guarantee their survival and sustain their aberrant evolution toward malignancy (Velichko et al, 2013).The Heat Shock Protein 90 (HSP90) is a highly conserved and ubiquitously expressed chaperone essential for cell survival
We recently found that Morgana is secreted by several cancer cells through an unconventional pathway and it associates with HSP90
We found that Toll-like receptor 4 (TLR4), TLR2, and lipoprotein receptor-related protein 1 (LRP1) are all required for eMorgana function (Figure 1C)
Summary
In order to survive and proliferate in a highly stressful environment cancer cells upregulate chaperone expression and actively release chaperones in the extracellular milieu to guarantee their survival and sustain their aberrant evolution toward malignancy (Velichko et al, 2013).The Heat Shock Protein 90 (HSP90) is a highly conserved and ubiquitously expressed chaperone essential for cell survival. Co-chaperones bind sequentially and reversibly to HSP90 to regulate its conformational changes, its ATPase activity and to confer specificity to clients. Hypoxia-inducible factor 1 alpha (HIF1α) stabilization in hypoxic conditions (Li et al, 2007; Sahu et al, 2012) and extracellular signal-regulated kinase (ERK) pathway activation in response to oxidative stress (Liao et al, 2000) are both able to stimulate HSP90 secretion.
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