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 PMID:19914164  

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

Maria Genander | Michael M Halford | Nan-Jie Xu | Malin Eriksson | Zuoren Yu | Zhaozhu Qiu | Anna Martling | Gedas Greicius | Sonal Thakar | Timothy Catchpole | Michael J Chumley | Sofia Zdunek | Chenguang Wang | Torbjörn Holm | Stephen P Goff | Sven Pettersson | Richard G Pestell | Mark Henkemeyer | Jonas Frisén
Cell | 2009

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.

Pubmed ID: 19914164

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA075503
  • Agency: NCI NIH HHS, United States
    Id: P30CA56036
  • Agency: NCI NIH HHS, United States
    Id: R01CA75503
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH066332-07
  • Agency: NCI NIH HHS, United States
    Id: R01 CA070896
  • Agency: NIMH NIH HHS, United States
    Id: 2R01 MH66332
  • Agency: NCI NIH HHS, United States
    Id: P30 CA056036
  • Agency: NCI NIH HHS, United States
    Id: R01CA70896
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH066332
  • Agency: NCI NIH HHS, United States
    Id: R01CA86072
  • Agency: NCI NIH HHS, United States
    Id: R01 CA086072

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