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Wnt-5a is one of the most highly investigated non-canonical Wnts and has been implicated in almost all aspects of non-canonical Wnt signalling. In terms of cancer development, Wnt-5a has, until recently, lived in the shadow of its better-characterised relatives. This was largely because of its apparent inability to transform cells or signal through the canonical beta-catenin pathway that is so important in cancer, particularly colorectal cancer. Recent work in a wide range of human tumours has pointed to a critical role for Wnt-5a in malignant progression, but there is conflicting evidence whether Wnt-5a has a tumour-promoting or -suppressing role. Emerging evidence suggests that the functions of Wnt-5a can be drastically altered depending on the availability of key receptors. Hence, the presence or absence of these receptors may go some way to explain the conflicting role of Wnt-5a in different cancers. This review summarises our current understanding of Wnt-5a and cancer.
Figure 1. An overview of Wnt-5a signalling. (A) Wnt-5a can activate PCP through a process dependent on Roh A and possibly Roh B leading to the control of cellular movement. (B) Wnt-5a uses numerous signalling molecules leading to the release of Ca2+ resulting in various cellular effects including cell movement and inhibition of the canonical Wnt signalling pathway. (C) Wnt-5a can bind the ROR-2 receptor activating JNK and the cytoskeleton as well as inhibiting β-catenin/TCF dependent transcription. (D) Wnt-5a can inhibit β-catenin/TCF-dependent transcription through Shia-1. (E) In the presence of FZ4 and LRP-5, Wnt-5a can activate β-catenin/TCF-dependent transcription. (F) Wnt-5a can activate PKA, which in turn can inhibit GSK-β to promote β-catenin/TCF-dependent transcription. Figure adapted from Semenov et al (2007).
Blanc,
Low expression of Wnt-5a gene is associated with high-risk neuroblastoma.
2005, Pubmed
Blanc,
Low expression of Wnt-5a gene is associated with high-risk neuroblastoma.
2005,
Pubmed
Brannon,
A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus.
1997,
Pubmed
,
Xenbase
Chien,
Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model.
2009,
Pubmed
Cleton-Jansen,
E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer?
2002,
Pubmed
Da Forno,
WNT5A expression increases during melanoma progression and correlates with outcome.
2008,
Pubmed
Dejmek,
Wnt-5a protein expression in primary dukes B colon cancers identifies a subgroup of patients with good prognosis.
2005,
Pubmed
Dejmek,
Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival.
2005,
Pubmed
Dissanayake,
The Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition.
2007,
Pubmed
Du,
Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos.
1995,
Pubmed
,
Xenbase
Ewan,
The potential for targeting oncogenic WNT/beta-catenin signaling in therapy.
2008,
Pubmed
Fernandez-Cobo,
Expression of Wnt5A and Wnt10B in non-immortalized breast cancer cells.
2007,
Pubmed
Giles,
Caught up in a Wnt storm: Wnt signaling in cancer.
2003,
Pubmed
Green,
Convergent extension and the hexahedral cell.
2007,
Pubmed
Huang,
Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor--an expression in non-small-cell lung cancer.
2005,
Pubmed
Ishitani,
The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.
2003,
Pubmed
Jones,
Planar cell polarity signaling in vertebrates.
2007,
Pubmed
Jönsson,
Loss of Wnt-5a protein is associated with early relapse in invasive ductal breast carcinomas.
2002,
Pubmed
Kremenevskaja,
Wnt-5a has tumor suppressor activity in thyroid carcinoma.
2005,
Pubmed
Kühl,
The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape.
2000,
Pubmed
Kühl,
Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus.
2000,
Pubmed
,
Xenbase
Kurayoshi,
Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion.
2006,
Pubmed
Liang,
Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue.
2003,
Pubmed
Liu,
Expression of Wnt-5a and its clinicopathological significance in hepatocellular carcinoma.
2008,
Pubmed
Ma,
Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway.
2007,
Pubmed
MacLeod,
Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells.
2007,
Pubmed
Major,
New regulators of Wnt/beta-catenin signaling revealed by integrative molecular screening.
2008,
Pubmed
Medrek,
Wnt-5a-CKI{alpha} signaling promotes {beta}-catenin/E-cadherin complex formation and intercellular adhesion in human breast epithelial cells.
2009,
Pubmed
Mikels,
Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context.
2006,
Pubmed
Mlodzik,
Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation?
2002,
Pubmed
Nomachi,
Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A.
2008,
Pubmed
Oishi,
The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway.
2003,
Pubmed
,
Xenbase
Pukrop,
Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines.
2006,
Pubmed
,
Xenbase
Qian,
Wnt5a functions in planar cell polarity regulation in mice.
2007,
Pubmed
,
Xenbase
Ripka,
WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer.
2007,
Pubmed
Roman-Gomez,
WNT5A, a putative tumour suppressor of lymphoid malignancies, is inactivated by aberrant methylation in acute lymphoblastic leukaemia.
2007,
Pubmed
Säfholm,
The Wnt-5a-derived hexapeptide Foxy-5 inhibits breast cancer metastasis in vivo by targeting cell motility.
2008,
Pubmed
Semenov,
SnapShot: Noncanonical Wnt Signaling Pathways.
2007,
Pubmed
Sheldahl,
Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos.
2003,
Pubmed
,
Xenbase
Shimizu,
Transformation by Wnt family proteins correlates with regulation of beta-catenin.
1997,
Pubmed
Slusarski,
Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A.
1997,
Pubmed
Slusarski,
Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling.
1997,
Pubmed
,
Xenbase
Torii,
Anti-apoptotic action of Wnt5a in dermal fibroblasts is mediated by the PKA signaling pathways.
2008,
Pubmed
Torres,
Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.
1996,
Pubmed
,
Xenbase
Veeman,
A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling.
2003,
Pubmed
Wallingford,
Convergent extension: the molecular control of polarized cell movement during embryonic development.
2002,
Pubmed
,
Xenbase
Wang,
Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer.
2007,
Pubmed
Weeraratna,
Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma.
2002,
Pubmed
Winkel,
Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated kinase-1) with the receptor tyrosine kinase Ror2 modulates canonical Wnt-signalling.
2008,
Pubmed
Witze,
Wnt5a control of cell polarity and directional movement by polarized redistribution of adhesion receptors.
2008,
Pubmed
Ying,
WNT5A exhibits tumor-suppressive activity through antagonizing the Wnt/beta-catenin signaling, and is frequently methylated in colorectal cancer.
2008,
Pubmed
Ying,
WNT5A is epigenetically silenced in hematologic malignancies and inhibits leukemia cell growth as a tumor suppressor.
2007,
Pubmed
