@article{aa0c04b203d8457690c0b78a3c981c94,
title = "Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression",
abstract = "Signaling proteins driving the proliferation of stem and progenitor cells are often encoded by proto-oncogenes. EphB receptors represent a rare exception; they promote cell proliferation in the intestinal epithelium and function as tumor suppressors by controlling cell migration and inhibiting invasive growth. We show that cell migration and proliferation are controlled independently by the receptor EphB2. EphB2 regulated cell positioning is kinase-independent and mediated via phosphatidylinositol 3-kinase, whereas EphB2 tyrosine kinase activity regulates cell proliferation through an Abl-cyclin D1 pathway. Cyclin D1 regulation becomes uncoupled from EphB signaling during the progression from adenoma to colon carcinoma in humans, allowing continued proliferation with invasive growth. The dissociation of EphB2 signaling pathways enables the selective inhibition of the mitogenic effect without affecting the tumor suppressor function and identifies a pharmacological strategy to suppress adenoma growth.",
keywords = "CELLBIO, HUMDISEASE, SIGNALING",
author = "Maria Genander and Halford, {Michael M.} and Xu, {Nan Jie} and Malin Eriksson and Zuoren Yu and Zhaozhu Qiu and Anna Martling and Gedas Greicius and Sonal Thakar and Timothy Catchpole and Chumley, {Michael J.} and Sofia Zdunek and Chenguang Wang and Torbj{\"o}rn Holm and Goff, {Stephen P.} and Sven Pettersson and Pestell, {Richard G.} and Mark Henkemeyer and Jonas Fris{\'e}n",
note = "Funding Information: We thank F. Granath, J. Holmberg, L. Huminiecki, J. Lindholm, A. Simon, and members of the Fris{\'e}n lab for valuable discussions, M.-L. Sp{\aa}ngberg and M. Toro for technical assistance, and Novartis for providing Gleevec and AEW-541. This study was supported by grants from the NIH (R01CA70896, R01CA75503, and R01CA86072 to R.G.P. and 2R01 MH66332 to M.H.), the Dr. Ralph and Marian C. Falk Medical Research Trust, the Pennsylvania Department of Health (which specifically disclaims responsibility for analyses, interpretations, or conclusions) (R.G.P.), the Swedish Cancer Society, the Swedish Research Council, Knut och Alice Wallenbergs Stiftelse, the Karolinska Institute, and the Tobias Foundation (J.F.). The Kimmel Cancer Center was supported by the NIH Cancer Center Core grant P30CA56036 (R.G.P). ",
year = "2009",
month = nov,
day = "13",
doi = "10.1016/j.cell.2009.08.048",
language = "English (US)",
volume = "139",
pages = "679--692",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}