Type

Journal Article

Authors

Jochen H M Prehn
Caoimhín G Concannon
Heiko Düssmann
Linda Williams
Franziska Walter
Tytus Bernas
Lavanya Ramapathiran

Subjects

Biochemistry

Topics
heat shock response ultrastructure metabolism humans colonic neoplasms hsp70 heat shock proteins hct116 cells genetics apoptosis time lapse imaging pathology single cell analysis cell survival

Single-cell imaging of the heat-shock response in colon cancer cells suggests that magnitude and length rather than time of onset determines resistance to apoptosis. (2013)

Abstract Targeting the proteasome is a valuable approach for cancer therapy, potentially limited by pro-survival pathways that are induced in parallel to cell death. Whether these pro-survival pathways are activated in all cells, show different activation kinetics in sensitive versus resistant cells or interact functionally with cell death pathways is unknown. We monitored activation of the heat-shock response (HSR), a key survival pathway induced by proteasome inhibition, relative to apoptosis activation in HCT116 colon cancer cells expressing enhanced green fluorescent protein (EGFP) under the control of the HSP70 promoter. Single-cell and high-content time-lapse imaging of epoxomicin treatment revealed that neither basal activity nor the time of onset of the HSR differed between resistant and sensitive populations. However, resistant cells had significantly higher and prolonged reporter activity than those that succumbed to cell death. p53 deficiency protected against cell death but failed to modulate the HSR. By contrast, inhibition of the HSR significantly increased the cytotoxicity of epoxomicin. Our data provide novel insights into the kinetics and heterogeneity of the HSR during proteasome inhibition, suggesting that the HSR modulates cell death signalling unidirectionally.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Caoimhín G Concannon, Heiko Düssmann, Linda Williams, Franziska Walter, Tytus Bernas, Lavanya Ramapathiran

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
3
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
 
4
Franziska Walter
Royal College of Surgeons in Ireland
Total Publications: 5
 
5
Tytus Bernas
Royal College of Surgeons in Ireland
Total Publications: 8