title: Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis.
abstract: Lung cancer is notorious for its ability to metastasize, but the pathways regulating lung cancer metastasis are largely unknown. An in vitro system designed to discover factors critical for lung cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosin-related kinase B (TrkB; also called NTRK2). Knockdown of TrkB in human lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. In an autochthonous lung adenocarcinoma model driven by activated oncogenic Kras and p53 loss, TrkB deficiency significantly reduced metastasis. Hypoxia-inducible factor-1 directly regulated TrkB expression, and, in turn, TrkB activated Akt signaling in metastatic lung cancer cells. Finally, TrkB expression was correlated with metastasis in patient samples, and TrkB was detected more often in tumors that did not have Kras or epidermal growth factor receptor mutations. These studies demonstrate that TrkB is an important therapeutic target in metastatic lung adenocarcinoma.
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Kerstin W
authors: KW
authors: Sinkevicius
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Christina
authors: C
authors: Kriegel
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Kelly J
authors: KJ
authors: Bellaria
authors: Department of Cell Biology and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115;
authors: Jaewon
authors: J
authors: Lee
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Allison N
authors: AN
authors: Lau
authors: Department of Pediatrics, Division of Newborn Medicine, Boston Children's Hospital Boston, Harvard Medical School, Boston, MA 02115;
authors: Kristen T
authors: KT
authors: Leeman
authors: Department of Pediatric Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115;Department of Neurobiology, Harvard Medical School, Boston, MA 02115;
authors: Pengcheng
authors: P
authors: Zhou
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Alexander M
authors: AM
authors: Beede
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Christine M
authors: CM
authors: Fillmore
authors: Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305;
authors: Deborah
authors: D
authors: Caswell
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors: Juliana
authors: J
authors: Barrios
authors: Department of Medical Oncology and Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115;Department of Medicine, Harvard Medical School, Boston, MA 02115;
authors: Kwok-Kin
authors: KK
authors: Wong
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors: Lynette M
authors: LM
authors: Sholl
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;
authors: Thorsten M
authors: TM
authors: Schlaeger
authors: Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA 02115; and.
authors: Roderick T
authors: RT
authors: Bronson
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors: Lucian R
authors: LR
authors: Chirieac
authors: Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305;Department of Genetics and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors: Monte M
authors: MM
authors: Winslow
authors: Department of Cell Biology and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115;
authors: Marcia C
authors: MC
authors: Haigis
authors: Stem Cell Program, Boston Children's Hospital, Boston MA 02115;Harvard Stem Cell Institute, Cambridge, MA 02138;Department of Genetics, Harvard Medical School, Boston, MA 02115; carla.kim@childrens.harvard.edu.
authors: Carla F
authors: CF
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008817:Mice, Mutant Strains; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051793:Hypoxia-Inducible Factor 1; D008562:Membrane Glycoproteins; C064371:Ntrk2 protein, mouse; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt
keywords: NSCLC; TrkB/NTRK2