Hsp70 inhibition induces myeloma cell death via the intracellular accumulation of immunoglobulin and the generation of proteotoxic stress

Cancer Lett. 2013 Oct 1;339(1):49-59. doi: 10.1016/j.canlet.2013.07.023. Epub 2013 Jul 22.

Abstract

Multiple myeloma (MM) cells rely on protein homeostatic mechanisms for survival. These mechanisms could be therapeutically targeted via modulation of the heat shock response. We studied the roles of Hsp72 and Hsc70, and show that the two major cytoplasmic Hsp70s play a key role in regulating protein homeostasis and controlling multiple oncogenic pathways in MM, and their inhibition can lead to myeloma cell death. Our study provides further evidence that targeting Hsp70 represents a novel therapeutic approach which may be effective in the treatment of MM.

Keywords: ER stress; Haematology; Hsp70; Multiple myeloma; Protein folding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / genetics
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Gene Silencing
  • HSC70 Heat-Shock Proteins / genetics
  • HSC70 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors
  • HSP70 Heat-Shock Proteins / genetics*
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Immunoglobulins / metabolism*
  • Intracellular Space / metabolism
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism*
  • RNA Interference
  • Stress, Physiological* / genetics
  • Ubiquitin / metabolism

Substances

  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Immunoglobulins
  • Ubiquitin