Overexpression of aberrant Wnt5a and its effect on acquisition of malignant phenotypes in adult T-cell leukemia/lymphoma (ATL) cells.
Cell Differentiation
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Deltaretrovirus
/ genetics
Gene Expression
/ genetics
Humans
Jurkat Cells
Leukemia-Lymphoma, Adult T-Cell
/ genetics
Phenotype
T-Lymphocytes
/ pathology
Wnt Signaling Pathway
/ genetics
Wnt-5a Protein
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 02 2021
18 02 2021
Historique:
received:
04
08
2020
accepted:
03
02
2021
entrez:
19
2
2021
pubmed:
20
2
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Wnt5a is a ligand of the non-canonical Wnt signaling pathway involved in cell differentiation, motility, and inflammatory response. Adult T-cell leukemia/lymphoma (ATL) is one of the most aggressive T-cell malignancies caused by infection of human T-cell leukemia virus type1 (HTLV-1). Among subtypes of ATL, acute-type ATL cells are particularly resistant to current multidrug chemotherapies and show remarkably high cell-proliferative and invasive phenotypes. Here we show a dramatic increase of WNT5A gene expression in acute-type ATL cells compared with those of indolent-type ATL cells. Treatment with IWP-2 or Wnt5a-specific knockdown significantly suppressed cell growth of ATL-derived T-cell lines. We demonstrated that the overexpression of c-Myb and FoxM1 was responsible for the synergistic activation of the WNT5A promoter. Also, a WNT5A transcript variant without the exon4 (the ΔE4-WNT5A mRNA), encoding ΔC-Wnt5 (1-136aa of 380aa), is overexpressed in acute-type ATL cells. The ΔC-Wnt5a is secreted extracellularly and enhances cellular migration/invasion to a greater extent compared with wildtype (WT)-Wnt5a. Moreover, the ΔC-Wnt5a secretion was not suppressed by IWP-2, indicating that this mutant Wnt5a is secreted via a different pathway from the WT-Wnt5a. Taken together, synergistic overexpression of the ΔC-Wnt5a by c-Myb and FoxM1 may be responsible for the malignant phenotype of acute-type ATL cells.
Identifiants
pubmed: 33603066
doi: 10.1038/s41598-021-83613-2
pii: 10.1038/s41598-021-83613-2
pmc: PMC7892546
doi:
Substances chimiques
WNT5A protein, human
0
Wnt-5a Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4114Références
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