CD133-positive cells are resistant to TRAIL due to up-regulation of FLIP.
Recent research shows that Cancer stem cells (CSCs) are relatively resistant to apoptosis induction. We studied the effect of the immunological apoptogen TRAIL on Jurkat cells enriched in the CD133-positive population. CD133(high) Jurkat cells were more resistant to apoptosis than their CD133(low) counterparts, and showed higher level of expression of FLIP, an inhibitor of death receptor-mediated apoptosis. Breast cancer MCF7 cells showed high level of expression CD133 in the unseparated culture, with accompanying high level of FLIP. Down-regulation of FLIP by siRNA resulted in sensitisation of the cells to TRAIL, as documented by more robust apoptosis. We conclude that high expression of FLIP is at least one of the reasons for resistance of CSCs to apoptosis induced by the death ligand TRAIL.
Zobalova
Renata
R
Apoptosis Research Group, School of Medical Science, Griffith Institute of Health and Medical Research, Griffith University Gold Coast Campus, Parklands Avenue, Southport, Qld, Australia.
McDermott
Laura
L
Stantic
Marina
M
Prokopova
Katerina
K
Dong
Lan-Feng
LF
Neuzil
Jiri
J
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human