Untangling the complexity of heat shock protein 27 in cancer and metastasis

Heat shock protein 27 is a type of molecular chaperone whose expression gets up-regulated due to reaction towards different stressful triggers including anticancer treatments. It is known to be a major player of resistance development in cancer cells, whereby cells are sheltered against the therapeutics that normally activate apoptosis. Heat shock protein 27 (HSP27) is one of the highly expressed proteins during various cellular insults and is a strong tumor survival factor. HSP27 influences various cellular pathways associated with cancer cell survival and growth such as apoptosis, autophagy, metastasis, angiogenesis, epithelial to mesenchymal transition, etc. HSP27 is molecular machinery which prevents the clumping of numerous substrates or client proteins which get mutated in cancer. It has been reported in several studies that targeting HSP27 is difficult because of its dynamic structure and absence of an ATP-binding site. Here, in this review, we have summarized different modulators of HSP27 and their mechanism of action as well. Effect of deregulated HSP27 in various cancer models, limitations of targeting HSP27, resistance against the conventional drugs generated due to the overexpression of HSP27, and measures to counteract this effect have also been discussed here in detail.