1. The mTOR inhibitor rapamycin synergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells
- Author
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Han Sheng, Chen Yan, Huang Wei, Yang Jingyue, Xue Yan, Liu Wen-chao, and Zheng Minjuan
- 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 - 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.
- Published
- 2013