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β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD
- Source :
- Experimental cell research. 346(1)
- Publication Year :
- 2016
-
Abstract
- Resistance to anthracycline based chemotherapy is a major limitation in the treatment of breast cancer, particularly of the triple negative sub-type that lacks targeted therapies. Resistance that arises from tumor-stromal interaction facilitated by integrins provides the possibility of targeted disruption. In the present study, we demonstrate that integrin β3 signaling inhibits apoptosis induced by a DNA-damaging chemotherapeutic agent, epirubicin, in MDA-MB-231 breast cancer cells. Drug efflux based mechanisms do not contribute to this effect. We show that integrin β3 employs the PI3K-Akt and the MAPK pathway for enabling cell survival and proliferation. Further, our results indicate that integrin β3 helps inhibit epirubicin induced cytotoxicity by repression of the pro-apoptotic protein BAD, thus promoting an anti-apoptotic response. Myristoylated RGT peptide and a monoclonal antibody against integrin β3 brought about a reversal of this effect and chemosensitized the cells. These results identify β3 integrin signaling via repression of BAD as an important survival pathway used by breast cancer cells to evade chemotherapy induced stress.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Anthracycline
medicine.drug_class
Cell Survival
Integrin
Apoptosis
Biology
Monoclonal antibody
Ligands
Myristic Acid
03 medical and health sciences
Inhibitory Concentration 50
0302 clinical medicine
Cell Line, Tumor
medicine
Humans
Cytotoxicity
Antibodies, Blocking
Psychological repression
Cell Proliferation
Epirubicin
Integrin beta3
Cell Biology
Flow Cytometry
Cell biology
030104 developmental biology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
biology.protein
bcl-Associated Death Protein
Collagen
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 346
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....a5ef071e28d3aa37490696c03ce93743