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EGFR/PPARδ/HSP90 pathway mediates cancer cell metabolism and chemoresistance
- Source :
- Journal of Cellular Biochemistry. 122:394-402
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Epidermal growth factor receptor (EGFR) induces peroxisome-proliferator-activated receptor-δ (PPARδ)-Y108 phosphorylation, while it is unclear the effect of phosphorylation of PPARδ on cancer cell metabolism. Here we found that EGF treatment increased its protein stability by inhibiting its lysosomal dependent degradation, which was reduced by gefitinib (EGFR inhibitor) treatment. PPARδ-Y108 phosphorylation in response to EGF recruited HSP90 (heat shock protein 90) to PPARδ resulting in increased PPARδ stability. In addition, PPARδ-Y108 phosphorylation promoted cancer cell metabolism, proliferation, and chemoresistance. Therefore, this study revealed a novel molecular mechanism of EGFR/HSP90/PPARδ pathway-mediated cancer cell metabolism, proliferation, and chemoresistance, which provides a strategy for cancer treatment.
- Subjects :
- 0301 basic medicine
Blotting, Western
Biochemistry
03 medical and health sciences
0302 clinical medicine
Gefitinib
medicine
Humans
Immunoprecipitation
HSP90 Heat-Shock Proteins
PPAR delta
Epidermal growth factor receptor
Phosphorylation
Receptor
Molecular Biology
Cell Proliferation
EGFR inhibitors
biology
Protein Stability
Chemistry
Cancer
Cell Biology
medicine.disease
Hsp90
ErbB Receptors
030104 developmental biology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
HT29 Cells
HeLa Cells
medicine.drug
Subjects
Details
- ISSN :
- 10974644 and 07302312
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....a02a7ea5826be01c633d5c539f9d130f