Please use this identifier to cite or link to this item:
https://doi.org/10.15252/emmm.201708313
Title: | Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer | Authors: | Ali, A Levantini, E Teo, J.T Goggi, J Clohessy, J.G Wu, C.S Chen, L Yang, H Krishnan, I Kocher, O Zhang, J Soo, R.A Bhakoo, K Chin, T.M Tenen, D.G |
Keywords: | epidermal growth factor receptor fatty acid synthase gefitinib protein tyrosine kinase inhibitor tetrahydrolipstatin EGFR protein, human epidermal growth factor receptor fatty acid fatty acid synthase protein kinase B protein kinase inhibitor tetrahydrolipstatin animal cell animal experiment animal model antineoplastic activity Article cancer inhibition cell cycle cell proliferation cell viability controlled study enzyme inhibition fatty acid metabolism female human human cell in vivo study male mouse non small cell lung cancer nonhuman palmitoylation priority journal signal transduction transgenic mouse tumor resistance tumor volume tumor xenograft ubiquitination animal antagonists and inhibitors biological model drug effect drug resistance drug screening gene expression regulation gene silencing genetics lipoylation lung tumor metabolism mutation non small cell lung cancer pathology tumor cell line upregulation Animals Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Cell Proliferation Drug Resistance, Neoplasm ErbB Receptors Fatty Acid Synthases Fatty Acids Gene Expression Regulation, Neoplastic Gene Silencing Lipoylation Lung Neoplasms Male Mice, Transgenic Models, Biological Mutation Orlistat Protein Kinase Inhibitors Proto-Oncogene Proteins c-akt Signal Transduction Ubiquitination Up-Regulation Xenograft Model Antitumor Assays |
Issue Date: | 2018 | Citation: | Ali, A, Levantini, E, Teo, J.T, Goggi, J, Clohessy, J.G, Wu, C.S, Chen, L, Yang, H, Krishnan, I, Kocher, O, Zhang, J, Soo, R.A, Bhakoo, K, Chin, T.M, Tenen, D.G (2018). Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer. EMBO Molecular Medicine 10 (3) : e8313. ScholarBank@NUS Repository. https://doi.org/10.15252/emmm.201708313 | Abstract: | Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug. Inhibition of FASN with Orlistat induces EGFR ubiquitination and abrogates EGFR mutant signaling, and reduces tumor growths both in culture systems and in vivo. Together, our data provide compelling evidence on the functional interrelationship between mutated EGFR and FASN and that the fatty acid metabolism pathway is a candidate target for acquired TKI-resistant EGFR mutant NSCLC patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license | Source Title: | EMBO Molecular Medicine | URI: | https://scholarbank.nus.edu.sg/handle/10635/173737 | ISSN: | 17574676 | DOI: | 10.15252/emmm.201708313 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_15252_emmm_201708313.pdf | 2.04 MB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.