Investigating the role of HSP90 in cancer cell phenotypic plasticity.

The emerging importance of epigenetic gene regulation in cancer progression necessitates not only our understanding of which genes are potential targets but also what mechanisms are employed in targeting those genes. Understanding the mechanisms that promote the evolution of the normal genome and epigenome is central to understanding how cancer cells adapt to chemotherapy. Our previous investigations have shown that heat shock protein 90 (HSP90) has a critical role in epigenetic gene regulation through histone acetylation and phenotypic plasticity. We recently extended these results in an A549 lung cancer model to test the role of HSP90 in the plasticity of cells regarding multi-drug resistance and epithelial-to-mesenchymal transition phenotypes. HSP90 is over-expressed in multiple cancers with poor prognosis. We propose that inhibition of HSP90 results in lower phenotypic plasticity of cancer cells making them more susceptible to chemotherapeutic intervention. Here we review the context of our results in the broader field of evolution of these phenotypes.