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The mTOR inhibitor rapamycin synergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 5, p e97697 (2014)
- Publication Year :
- 2013
-
Abstract
- Patients with ER/HER2-positive breast cancer have a poor prognosis and are less responsive to selective estrogen receptor modulators; this is presumably due to the crosstalk between ER and HER2. Fatty acid synthase (FASN) is essential for the survival and maintenance of the malignant phenotype of breast cancer cells. An intimate relationship exists between FASN, ER and HER2. We hypothesized that FASN may be the downstream effector underlying ER/HER2 crosstalk through the PI3K/AKT/mTOR pathway in ER/HER2-positive breast cancer. The present study implicated the PI3K/AKT/mTOR pathway in the regulation of FASN expression in ER/HER2-positive breast cancer cells and demonstrated that rapamycin, an mTOR inhibitor, inhibited FASN expression. Cerulenin, a FASN inhibitor, synergized with rapamycin to induce apoptosis and inhibit cell migration and tumorigenesis in ER/HER2-positive breast cancer cells. Our findings suggest that inhibiting the mTOR-FASN axis is a promising new strategy for treating ER/HER2-positive breast cancer.
- Subjects :
- Cell signaling
Receptor, ErbB-2
Physiology
Papillary Carcinomas
Tumor Physiology
Cancer Treatment
lcsh:Medicine
Invasive Ductal Carcinoma
Apoptosis
Signal transduction
medicine.disease_cause
Biochemistry
chemistry.chemical_compound
Mice
Benign Breast Tumors
Endocrinology
Cell Movement
Molecular Cell Biology
Basic Cancer Research
Breast Tumors
Tumor Cells, Cultured
Morphogenesis
Medicine and Health Sciences
Membrane Receptor Signaling
AKT signaling cascade
lcsh:Science
skin and connective tissue diseases
Fluorescent Antibody Technique, Indirect
Multidisciplinary
biology
Cell Death
Reverse Transcriptase Polymerase Chain Reaction
Signaling cascades
Drug Synergism
Gene Therapy
Hormone Receptor Signaling
Fatty Acid Synthase, Type I
Gene Expression Regulation, Neoplastic
Fatty acid synthase
Cell Motility
Ductal Carcinoma in Situ
Oncology
Selective estrogen receptor modulator
Cell Processes
Female
Invasive Lobular Carcinoma
Research Article
medicine.medical_specialty
Cell biology
Blotting, Western
Mice, Nude
Nipple Tumors
Breast Neoplasms
Cell Migration
Real-Time Polymerase Chain Reaction
Breast cancer
Internal medicine
medicine
Animals
Humans
RNA, Messenger
Molecular Biology Techniques
Protein kinase B
neoplasms
Protein Kinase Inhibitors
Molecular Biology
PI3K/AKT/mTOR pathway
Cell Proliferation
Sirolimus
Biology and life sciences
Endocrine Physiology
business.industry
lcsh:R
Estrogen Receptor alpha
Cancers and Neoplasms
medicine.disease
Xenograft Model Antitumor Assays
Cerulenin
Hormones
chemistry
biology.protein
Cancer research
lcsh:Q
business
Carcinogenesis
Developmental Biology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....90d3e0a7f568d9e9968ae82085a7d396