Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Heat Stress Induces Epithelial Plasticity and Cell Migration Independent of Heat Shock Factor 1. (#136)

Benjamin J Lang 1 , Linh Nguyen 2 , Chau Hoang Nguyen 1 , Jessica L Vieusseux 1 , Ryan C.C. Chai 1 , Christopher Christophi 2 , Theodora Fifis 2 , Michelle M Kouspou 1 , John T Price 1
  1. Monash University, Clayton, VIC, Australia
  2. Department of Surgery, The University of Melbourne, Heidelberg, Victoria, Australia

The Heat Shock Response (HSR) is a major cellular stress pathway activated by protein-damaging (proteotoxic) stress. Both proteotoxic stress and HSR activation are inherent to cancer cells and cancer therapies including cytotoxic chemotherapy, radiation and hyperthermic therapy. The current study examines the concept that tumour cell exposure to acute proteotoxic stress results in the acquisition of a more advanced and aggressive cancer cell phenotype through activation of the transcriptional regulator of the HSR, Heat Shock Factor-1 (HSF1). Specifically, we determined whether heat stress resulted in an epithelial-to-mesenchymal transition (EMT) and/or the enhancement of cell migration, components of advanced and therapeutically resistant cancer phenotypes. We identified that heat stress enhanced cell migration in the lung A549, and breast MDA-MB-468 human adenocarcinoma cell lines, with A549 cells also undergoing a partial EMT. Moreover, in an in vivo model of thermally ablated liver metastases of the mouse colorectal MoCR cell line, immunohistological analysis of classical EMT markers demonstrated a shift to a mesenchymal phenotype in the surviving tumour fraction, further demonstrating that thermal stress can induce epithelial plasticity. However, despite HSF1 being the master regulator of the HSR, knockdown of HSF1 in the A549 model did not prevent the associated morphological changes or enhanced migratory profile of heat stressed cells. Therefore, this study provides evidence that heat stress significantly impacts upon cancer cell epithelial plasticity and the migratory phenotype independent of HSF1. These findings further our understanding of novel biological downstream effects of heat stress and their potential independence from the classical heat shock pathway.