The opposing roles of Wnt-5a in cancer - PubMed (original) (raw)

Review

The opposing roles of Wnt-5a in cancer

S L McDonald et al. Br J Cancer. 2009.

Abstract

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.

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Figures

Figure 1

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).

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References

    1. Blanc E, Roux GL, Benard J, Raguenez G (2005) Low expression of Wnt-5a gene is associated with high-risk neuroblastoma. Oncogene 24: 1277–1283 - PubMed
    1. Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D (1997) A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev 11: 2359–2370 - PMC - PubMed
    1. Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT (2009) Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc Natl Acad Sci USA 106: 1193–1198 - PMC - PubMed
    1. Cleton-Jansen AM (2002) E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer? Breast Cancer Res 4: 5–8 - PMC - PubMed
    1. Da Forno PD, Pringle JH, Hutchinson P, Osborn J, Huang Q, Potter L, Hancox RA, Fletcher A, Saldanha GS (2008) WNT5A expression increases during melanoma progression and correlates with outcome. Clin Cancer Res 14: 5825–5832 - PubMed

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