TRAIL induces endocytosis of its death receptors in MDA-MB-231 breast cancer cells

Cancer Biol Ther. 2009 May;8(10):917-22. doi: 10.4161/cbt.8.10.8141. Epub 2009 May 9.

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that selectively induces apoptosis in cancer cells over normal cells. Here, we show that TRAIL undergoes rapid endocytosis with its death receptors DR4, and likely DR5, in MDA-MB-231 human breast cancer cells. The internalized DR4, but not DR5, is cleaved in a caspase-dependent manner. Blockade of receptor internalization does not prevent caspase activation, but rather enhances apoptosis after TRAIL treatment. TRAIL-induced receptor endocytosis appears to undermine its ability in inducing apoptosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Female
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Kinetics
  • Phycoerythrin / metabolism
  • Plasmids / genetics
  • Receptors, Death Domain / genetics*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Temperature
  • Time Factors
  • Transfection

Substances

  • Receptors, Death Domain
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Phycoerythrin
  • Green Fluorescent Proteins