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

Research output: Contribution to journalArticle

109 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)679-692
Number of pages14
JournalCell
Volume139
Issue number4
DOIs
StatePublished - Nov 13 2009

Fingerprint

EphB2 Receptors
Cell proliferation
Tumors
Stem Cells
Cyclin D1
Cell Proliferation
Adenoma
Cell Movement
Growth
Eph Family Receptors
Phosphatidylinositol 3-Kinase
Neoplasms
Proto-Oncogenes
Intestinal Mucosa
Colon
Phosphotransferases
Pharmacology
Carcinoma
Proteins

Keywords

  • CELLBIO
  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Genander, M., Halford, M. M., Xu, N. J., Eriksson, M., Yu, Z., Qiu, Z., ... Frisén, J. (2009). Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression. Cell, 139(4), 679-692. https://doi.org/10.1016/j.cell.2009.08.048

Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression. / Genander, Maria; Halford, Michael M.; Xu, Nan Jie; Eriksson, Malin; Yu, Zuoren; Qiu, Zhaozhu; Martling, Anna; Greicius, Gedas; Thakar, Sonal; Catchpole, Timothy; Chumley, Michael J.; Zdunek, Sofia; Wang, Chenguang; Holm, Torbjörn; Goff, Stephen P.; Pettersson, Sven; Pestell, Richard G.; Henkemeyer, Mark; Frisén, Jonas.

In: Cell, Vol. 139, No. 4, 13.11.2009, p. 679-692.

Research output: Contribution to journalArticle

Genander, M, Halford, MM, Xu, NJ, Eriksson, M, Yu, Z, Qiu, Z, Martling, A, Greicius, G, Thakar, S, Catchpole, T, Chumley, MJ, Zdunek, S, Wang, C, Holm, T, Goff, SP, Pettersson, S, Pestell, RG, Henkemeyer, M & Frisén, J 2009, 'Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression', Cell, vol. 139, no. 4, pp. 679-692. https://doi.org/10.1016/j.cell.2009.08.048
Genander, Maria ; Halford, Michael M. ; Xu, Nan Jie ; Eriksson, Malin ; Yu, Zuoren ; Qiu, Zhaozhu ; Martling, Anna ; Greicius, Gedas ; Thakar, Sonal ; Catchpole, Timothy ; Chumley, Michael J. ; Zdunek, Sofia ; Wang, Chenguang ; Holm, Torbjörn ; Goff, Stephen P. ; Pettersson, Sven ; Pestell, Richard G. ; Henkemeyer, Mark ; Frisén, Jonas. / Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression. In: Cell. 2009 ; Vol. 139, No. 4. pp. 679-692.
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