Formation of the IGF1R/CAV1/SRC tri-complex antagonizes TRAIL-induced apoptosis in gastric cancer cells.
Cell Biol Int
; 41(7): 749-760, 2017 Jul.
Article
in En
| MEDLINE
| ID: mdl-28403518
ABSTRACT
Lipid rafts provide a biological platform for apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We previously reported that insulin-like growth factor 1 receptor (IGF1R) translocation into lipid rafts helped to explain TRAIL resistance. However, it was not clear whether TRAIL resistance was caused by the interaction of IGF1R with caveolin-1 (CAV1) and the non-receptor tyrosine kinase SRC in lipid rafts of gastric cancer cells. Here, we observed high IGF1R expression in TRAIL-resistant gastric cancer cells, and showed that IGF1R combined with both CAV1 and SRC in a native complex. TRAIL was shown to promote the formation of the IGF1R/CAV1/SRC tri-complex and the activation of these three molecules. Knockdown of IGF1R or CAV1 or inhibition of SRC activity reduced the formation of this tri-complex and enhanced TRAIL-induced apoptosis. Furthermore, the overexpression of microRNA-194 reversed TRAIL resistance by reducing IGF1R expression. In summary, TRAIL increased formation of the IGF1R/CAV1/SRC tri-complex and the activation of downstream survival pathways, leading to TRAIL resistance in gastric cancer cells.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Receptors, Somatomedin
/
Apoptosis
/
Src-Family Kinases
/
Caveolin 1
/
TNF-Related Apoptosis-Inducing Ligand
Limits:
Humans
Language:
En
Journal:
Cell Biol Int
Year:
2017
Type:
Article
Affiliation country:
China