The Proteostasis Network in Breast Cancer Cell Lines



Cancer cells are exposed to an array of stresses, including oxygen and glucose deprivation, low pH, and the over-production of misfolded proteins and orphaned protein subunits. Consequently, cancer cells must maintain high levels of molecular chaperones, which help maintain cellular protein homeostasis ("proteostasis"). Recent data indicate that different cancer cells exhibit different sensitivities to an inhibitor of Hsp70, which is the primary molecular chaperone in the cytoplasm.  One model is that these cells, in turn, exhibit differences in the extent of endoplasmic reticulum stress.  A test of this hypothesis has benefited from an ongoing collaboration between Dr. Jeff Brodsky in the Department of  Biological Sciences and the UPDDI, which has aided our understanding of why different cancers differentially require unique chaperone activities.

Combined chemical–genetic approach identifies cytosolic HSP70 dependence in rhabdomyosarcoma