Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue.
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.
Liang
Huiling
H
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Chen
Qin
Q
Coles
Andrew H
AH
Anderson
Stephen J
SJ
Pihan
German
G
Bradley
Allan
A
Gerstein
Rachel
R
Jurecic
Roland
R
Jones
Stephen N
SN
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D005434:Flow Cytometry; D006413:Hematopoietic System / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D019656:Loss of Heterozygosity / Q000502:physiology; D008221:Lymphoid Tissue / Q000503:physiopathology; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014183:Transplantation, Heterologous; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D019938:Cyclin D1; D002118:Calcium