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Sci. Signal., 5 March 2013
Vol. 6, Issue 265, p. ra14
[DOI: 10.1126/scisignal.2003398]


Editor's Summary

Releasing β-Catenin for Melanoma Metastasis
Signaling through the Wnt pathway stimulates gene transcription mediated by β-catenin, and nuclear β-catenin is associated with a poor prognosis in cancer. The amount of β-catenin that is available to transcriptionally activate Wnt target genes may depend on the amount that is bound by cadherin in cell-cell adhesion structures called adherens junctions. Grossmann et al. found that WNT5A, which was produced by various melanoma cell lines, activated the small guanosine triphosphatase ARF6, triggered the release of β-catenin from N-cadherin, and increased the transcriptional activity of β-catenin. Pharmacological inhibition of ARF6 reduced β-catenin activity and invasive activity of melanoma cells in culture and decreased pulmonary metastasis in mice with tumors formed from melanoma cells. Thus, ARF6 may be a viable therapeutic target for reducing the invasiveness and metastasis of melanomas.

Citation: A. H. Grossmann, J. H. Yoo, J. Clancy, L. K. Sorensen, A. Sedgwick, Z. Tong, K. Ostanin, A. Rogers, K. F. Grossmann, S. R. Tripp, K. R. Thomas, C. D’Souza-Schorey, S. J. Odelberg, D. Y. Li, The Small GTPase ARF6 Stimulates β-Catenin Transcriptional Activity During WNT5A-Mediated Melanoma Invasion and Metastasis. Sci. Signal. 6, ra14 (2013).

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WNT5A-mediated {beta}-catenin-independent signalling is a novel regulator of cancer cell metabolism.
V. Sherwood, S. K. Chaurasiya, E. J. Ekstrom, W. Guilmain, Q. Liu, T. Koeck, K. Brown, K. Hansson, M. Agnarsdottir, M. Bergqvist, et al. (2014)
Carcinogenesis 35, 784-794
   Abstract »    Full Text »    PDF »
Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2.
M. P. O'Connell, K. Marchbank, M. R. Webster, A. A. Valiga, A. Kaur, A. Vultur, L. Li, M. Herlyn, J. Villanueva, Q. Liu, et al. (2013)
Cancer Discovery 3, 1378-1393
   Abstract »    Full Text »    PDF »
ARF6-Regulated Endocytosis of Growth Factor Receptors Links Cadherin-Based Adhesion to Canonical Wnt Signaling in Epithelia.
O. Pellon-Cardenas, J. Clancy, H. Uwimpuhwe, and C. D'Souza-Schorey (2013)
Mol. Cell. Biol. 33, 2963-2975
   Abstract »    Full Text »    PDF »
A Wnt-er Migration: The Confusing Role of {beta}-Catenin in Melanoma Metastasis.
M. R. Webster and A. T. Weeraratna (2013)
Science Signaling 6, pe11
   Abstract »    Full Text »    PDF »

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