Back to Search
Start Over
Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals
- Source :
- FEBS letters. 583(13)
- Publication Year :
- 2009
-
Abstract
- The present study reported that the ubiquitin ligase Cbl-b was up-regulated during anthracycline-induced apoptosis in two cell lines, RBL-2H3 leukemia cells and MGC803 gastric cancer cells. Overexpression of Cbl-b strongly promoted the cytotoxic and apoptosis-inducing effects of anthracyclines, while a dominant negative (DN) Cbl-b mutation abolished these effects in both cell lines. Further investigation revealed that mitochondrial depolarization was enhanced by Cbl-b and decreased by Cbl-b (DN) in RBL-2H3 cells. Moreover, overexpression of Cbl-b significantly suppressed ERK activation, and Cbl-b (DN) strongly enhanced both ERK and Akt activation. Altogether, these results indicate that Cbl-b sensitized both leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial apoptotic pathway and modulating the ERK and Akt survival pathways.
- Subjects :
- MAPK/ERK pathway
Biophysics
Anthracycline
Transfection
Biochemistry
environment and public health
Structural Biology
Stomach Neoplasms
hemic and lymphatic diseases
Cell Line, Tumor
Genetics
medicine
Cytotoxic T cell
Animals
Humans
Anthracyclines
Proto-Oncogene Proteins c-cbl
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Protein kinase B
PI3K/Akt
Antibiotics, Antineoplastic
Leukemia
biology
Chemistry
fungi
Cell Biology
medicine.disease
Molecular biology
Ubiquitin ligase
Mitochondria
Rats
enzymes and coenzymes (carbohydrates)
ERK
Cell Transformation, Neoplastic
Apoptosis
Cbl-b
Cancer cell
Mutation
biology.protein
Cancer research
Gastric cancer
Proto-Oncogene Proteins c-akt
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- ISSN :
- 18733468
- Volume :
- 583
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- FEBS letters
- Accession number :
- edsair.doi.dedup.....eaf415c2ce0846e2a75b475b12ceafd5