Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first. 

Paper Chase

Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis.

Proc. Natl. Acad. Sci. U.S.A.. Jul 15, 2014;111(28):10299-304.
Sinkevicius KW, Kriegel C, Bellaria KJ, Lee J, Lau AN, Leeman KT, Zhou P, Beede AM, Fillmore CM, Caswell D, Barrios J, Wong KK, Sholl LM, Schlaeger TM, Bronson RT, Chirieac LR, Winslow MM, Haigis MC, Kim CF.

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.

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.