Document Detail


Heat stress induces epithelial plasticity and cell migration independent of heat shock factor 1.
MedLine Citation:
PMID:  22791010     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Current cancer therapies including cytotoxic chemotherapy, radiation and hyperthermic therapy induce acute proteotoxic stress in tumour cells. A major challenge to cancer therapeutic efficacy is the recurrence of therapy-resistant tumours and how to overcome their emergence. 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. Specifically, we determined whether heat stress resulted in an epithelial-to-mesenchymal transition (EMT) and/or the enhancement of cell migration, components of an advanced and therapeutically resistant cancer phenotype. We identified that heat stress enhanced cell migration in both 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 more mesenchymal phenotype in the surviving tumour fraction, further demonstrating that thermal stress can induce epithelial plasticity. To identify a mechanism by which thermal stress modulates epithelial plasticity, we examined whether the major transcriptional regulator of the heat shock response, heat shock factor 1 (HSF1), was a required component. 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.
Authors:
B J Lang; L Nguyen; H C Nguyen; J L Vieusseux; R C C Chai; C Christophi; T Fifis; M M Kouspou; John T Price
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-13
Journal Detail:
Title:  Cell stress & chaperones     Volume:  17     ISSN:  1466-1268     ISO Abbreviation:  Cell Stress Chaperones     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-11     Completed Date:  2013-03-05     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9610925     Medline TA:  Cell Stress Chaperones     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  765-78     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / metabolism
Cell Line, Tumor
Cell Movement
DNA-Binding Proteins / antagonists & inhibitors,  genetics,  metabolism*
Epithelial-Mesenchymal Transition
HSP110 Heat-Shock Proteins / metabolism
HSP27 Heat-Shock Proteins / metabolism
HSP70 Heat-Shock Proteins / metabolism
Humans
Immunohistochemistry
Mice
RNA Interference
RNA, Small Interfering / metabolism
Temperature
Transcription Factors / antagonists & inhibitors,  genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Cadherins; 0/DNA-Binding Proteins; 0/HSP110 Heat-Shock Proteins; 0/HSP27 Heat-Shock Proteins; 0/HSP70 Heat-Shock Proteins; 0/HSPA12A protein, human; 0/HSPB1 protein, human; 0/HSPH1 protein, human; 0/RNA, Small Interfering; 0/Transcription Factors; 0/heat shock transcription factor
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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