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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.

SUBMITTER: Genander M

PROVIDER: S-EPMC2786256 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression.

Genander Maria M Halford Michael M MM Xu Nan-Jie NJ Eriksson Malin M Yu Zuoren Z Qiu Zhaozhu Z Martling Anna A Greicius Gedas G Thakar Sonal S Catchpole Timothy T Chumley Michael J MJ Zdunek Sofia S Wang Chenguang C Holm Torbjörn T Goff Stephen P SP Pettersson Sven S Pestell Richard G RG Henkemeyer Mark M Frisén Jonas J

Cell 20091101 4

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 phosphatidylinosit ...[more]

PMID: 19914164

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Dataset Information

Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression.

Publications

Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression.

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