title: The mTOR inhibitor rapamycin synergizes with a fatty acid synthase inhibitor to induce cytotoxicity in ER/HER2-positive breast cancer cells.
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.
authors.affiliation: Department of Oncology, Xi'jing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Xi'jing hospital, Fourth military medical university, Xi'an, PR China.
authors.forename: Huang
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Ultrasound, Xi'jing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Minjuan
authors.affiliation: Department of Oncology, Xi'jing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Oncology, Xi'jing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jingyue
authors.affiliation: Department of Oncology, Xi'jing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Wenchao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Information Center, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Sheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002569:Cerulenin / Q000494:pharmacology; D004357:Drug Synergism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D002569:Cerulenin; D047628:Estrogen Receptor alpha; D054890:Fatty Acid Synthase, Type I; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020123:Sirolimus; C506487:ESR1 protein, human; C518729:FASN protein, human; C508053:ERBB2 protein, human