Noncanonical Wnt signaling promotes apoptosis in thymocyte development

Liang, Huiling; Coles, Andrew H.; Zhu, Zhenbo; Zayas, Jennifer; Jurecic, Roland; Kang, Joonsoo; Jones, Stephen N.

doi:10.1083/jcb1796oia17

Cited by 15 publications

(19 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 In a study on T cells, Wnt5a overexpression increased apoptosis and increased PKC and calmodulin-dependent kinase II (CamKII) activity in a manner antagonistic to canonical WNT signaling. 20 On the basis of previous studies, multiple functions of Wnt5a are PKC dependent. Protein kinase C is also overexpressed in ovarian cancer and is related to poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer

Peng

Zhang

et al. 2011

International Journal of Gynecological Cancer

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer

Peng

Zhang

et al. 2011

International Journal of Gynecological Cancer

View full text Add to dashboard Cite

show abstract

“…A number of studies suggest Wnt5a utilizes non-canonical and Ca ++ signaling pathways (25,56). Furthermore, it can oppose and even reverse canonical Wnt signaling in hematopoietic cells (26–28). Particularly interesting in this regard is the ability of Wnt5a to down-regulate β-catenin and thus inhibit T lymphopoiesis (26).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it can oppose and even reverse canonical Wnt signaling in hematopoietic cells (26–28). Particularly interesting in this regard is the ability of Wnt5a to down-regulate β-catenin and thus inhibit T lymphopoiesis (26). Again, this suggests how Wnt family molecules can function as counter-acting regulators and participate in lineage fate decisions.…”

Section: Discussionmentioning

confidence: 99%

“…Lymphopoietic abnormalities were intrinsic to hematopoietic cells in Wnt5a −/− mice, even though BM stroma of recipient mice expressed this factor. Further, thymocytes, and distal limb buds from Wnt5a −/− mice show increased canonical signaling, suggesting that Wnt5a opposes this pathway in normal situations (26,27). Another recent study concluded that Wnt5a can antagonize Wnt3a responses and maintain stem cells in a quiescent G0 state (28).…”

Section: Introductionmentioning

confidence: 99%

“…A case has also been made for Wnt contributions to T lymphopoiesis (26,30–37). As just one example, over-expression of the Wnt antagonist Dkk1, which prevents ligand-Fzd interaction, blocked T cell formation in fetal thymic organ cultures and blocked development at the double negative-1 (DN1) stage (33).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Contrasting Responses of Lymphoid Progenitors to Canonical and Noncanonical Wnt Signals

Malhotra

Baba

Garrett

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

The Wnt family of secreted glycoproteins has been implicated in many aspects of development, but its contribution to blood cell formation is controversial. We overexpressed Wnt3a, Wnt5a, and Dickkopf 1 in stromal cells from osteopetrotic mice and used them in coculture experiments with highly enriched stem and progenitor cells. The objective was to learn whether and how particular stages of B lymphopoiesis are responsive to these Wnt family ligands. We found that canonical Wnt signaling, through Wnt3a, inhibited B and plasmacytoid dendritic cell, but not conventional dendritic cell development. Wnt5a, which can oppose canonical signaling or act through a different pathway, increased B lymphopoiesis. Responsiveness to both Wnt ligands diminished with time in culture and stage of development. That is, only hematopoietic stem cells and very primitive progenitors were affected. Although Wnt3a promoted retention of hematopoietic stem cell markers, cell yields and dye dilution experiments indicated it was not a growth stimulus. Other results suggest that lineage instability results from canonical Wnt signaling. Lymphoid progenitors rapidly down-regulated RAG-1, and some acquired stem cell-staining characteristics as well as myeloid and erythroid potential when exposed to Wnt3a-producing stromal cells. We conclude that at least two Wnt ligands can differentially regulate early events in B lymphopoiesis, affecting entry and progression in distinct differentiation lineages.

show abstract

Wnt5a Suppresses Colon Cancer by Inhibiting Cell Proliferation and Epithelial–Mesenchymal Transition

Cheng

Sun

et al. 2014

Journal Cellular Physiology

View full text Add to dashboard Cite

Colon cancer remains one of the lethal malignancies in the world. Aberrant activation of canonical Wnt/β-catenin signaling pathway has been observed in colon cancer. In contrast, the non-canonical Wnt signaling functions remain obscure. Wnt5a is a representative non-canonical Wnt ligand which has gained extensive attention nowadays. Wnt5a has been shown to play an important role in EMT in prostate cancer and melanoma, but its role in colon cancer is still ambiguous. Here we have evaluated Wnt5a expression in a large cohort of 217 colon cancers by immunohistochemistry and analyzed its correlation with clinicopathologic characteristics. We found that expression of Wnt5a was diminished significantly in majority of primary colon cancers and negatively related with EMT biomarkers. To further enlighten the mechanism which Wnt5a regulates EMT in vitro, we established ectopic Wnt5a expression models. Protein analysis demonstrated that Wnt5a inhibited EMT and antagonized canonical Wnt signaling in colon cancer cells. Overexpression of Wnt5a impaired cell motility and invasion and inhibited cell proliferation by manipulating Bax. Moreover, Wnt5a suppressed the tumor growth in nude mice and impaired tumorigenicity in vivo. Wnt5a also induced intracellular calcium and activated non-canonical Wnt/Ca(2+) signaling in colon cancer. In summary, although Wnt5a was down-regulated in majority of colon cancers, enhanced Wnt5a expression predict preferable outcome in colon cancer patients. Our findings indicate that Wnt5a might act as tumor suppressor by inhibiting cell proliferation and attenuating EMT in colon cancer cells. Wnt5a could be used as a novel prognostic marker and/or therapeutic target for colon cancer in the future.

show abstract

Noncanonical Wnt signaling promotes apoptosis in thymocyte development

Cited by 15 publications

References 13 publications

Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer

Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer

Contrasting Responses of Lymphoid Progenitors to Canonical and Noncanonical Wnt Signals

Wnt5a Suppresses Colon Cancer by Inhibiting Cell Proliferation and Epithelial–Mesenchymal Transition

Contact Info

Product

Resources

About