Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue

Huiling Liang, Qin Chen, Andrew H. Coles, Stephen J. Anderson, German Pihan, Allan Bradley, Rachel Gerstein, Roland Jurecic, Stephen N. Jones

Research output: Contribution to journalArticle

253 Scopus citations

Abstract

Wnt5a is a member of the Wnt family of secreted glycoproteins that play essential organizing roles in development. Similar to other Wnt members, Wnt5a can upregulate cell proliferation and has been proposed to have oncogenic function. Here we report that Wnt5a signals through the noncanonical Wnt/Ca ++ pathway to suppress cyclin D1 expression and negatively regulate B cell proliferation in a cell-autonomous manner. Wnt5a hemizygous mice develop myeloid leukemias and B cell lymphomas that are clonal in origin and display loss of Wnt5a function in tumor tissues. Furthermore, analysis of human primary leukemias reveals deletion of the WNT5A gene and/or loss of WNT5A expression in a majority of the patient samples. These results demonstrate that Wnt5a suppresses hematopoietic malignancies.

Original languageEnglish (US)
Pages (from-to)349-360
Number of pages12
JournalCancer Cell
Volume4
Issue number5
DOIs
StatePublished - Nov 2003

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Liang, H., Chen, Q., Coles, A. H., Anderson, S. J., Pihan, G., Bradley, A., Gerstein, R., Jurecic, R., & Jones, S. N. (2003). Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell, 4(5), 349-360. https://doi.org/10.1016/S1535-6108(03)00268-X