title: AURKA upregulation plays a role in fibroblast-reduced gefitinib sensitivity in the NSCLC cell line HCC827.
abstract: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat non-small cell lung carcinoma (NSCLC) patients that have EGFR-activating mutations. EGFR-TKI monotherapy in most NSCLC patients with EGFR mutations who initially respond to EGFR-TKIs results in the development of acquired resistance. We investigated the role of fibroblasts in stromal cell-mediated resistance to gefitinib-induced apoptosis in EGFR-mutant NSCLC cells. While gefitinib induced apoptosis in EGFR-mutant NSCLC cells, apoptosis induction was diminished under stromal co-culture conditions. Protection appeared to be mediated in part by Aurora-A kinase (AURKA) upregulation. The protective effect of stromal cells was significantly reduced by pre-exposure to AURKA-shRNA. We suggest that combinations of AURKA antagonists and EGFR inhibitors may be effective in clinical trials targeting mutant EGFR NSCLCs.
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Jia
authors: J
authors: Chen
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Huiqi
authors: H
authors: Lu
authors: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China.
authors: Wang
authors: W
authors: Zhou
authors: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China.
authors: Huabin
authors: H
authors: Yin
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Lishuang
authors: L
authors: Zhu
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Chang
authors: C
authors: Liu
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Pengfei
authors: P
authors: Zhang
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Huimin
authors: H
authors: Hu
authors: Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD, USA.
authors: Yili
authors: Y
authors: Yang
authors: Translational Medicine Center, Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai, P.R. China.
authors: Huanxing
authors: H
authors: Han
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D064096:Aurora Kinase A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D066246:ErbB Receptors / Q000172:deficiency; D005347:Fibroblasts / Q000201:enzymology*; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D017154:Stromal Cells / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C512478:EGFR protein, human; D066246:ErbB Receptors; C576917:AURKA protein, human; D064096:Aurora Kinase A; D000077156:Gefitinib
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