TRAIL induces endocytosis of its death receptors in MDA-MB-231 breast cancer cells.
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.
Zhang
Yaqin
Y
Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Yoshida
Tatsushi
T
Zhang
Baolin
B
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010799:Phycoerythrin / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D053218:Receptors, Death Domain / Q000235:genetics*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors; D014162:Transfection
D053218:Receptors, Death Domain; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D010799:Phycoerythrin; D049452:Green Fluorescent Proteins