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Sci. Signal., 10 January 2012
Vol. 5, Issue 206, p. ra3
Death to Melanoma
Melanoma is a particularly aggressive form of skin cancer. Although the identification of a specific mutation in the kinase-encoding gene BRAF has facilitated the development of clinical therapies, many melanoma patients with the BRAFV600E mutation fail to exhibit long-term responsiveness to inhibition of this kinase. Biechele et al. found that some melanoma cell lines exhibited an enhanced apoptotic response when BRAFV600E was inhibited simultaneously with activation of the Wnt/β-catenin pathway. The susceptibility to this cell death response correlated with the ability of the combination treatment to reduce the abundance of AXIN1, a negative regulator of the Wnt/β-catenin pathway, and knockdown of AXIN1 abundance caused apoptosis-resistant melanoma cell lines to become susceptible to apoptosis in response to the combined treatment. Thus, exploiting this functional crosstalk between BRAF and Wnt/β-catenin signaling may yield more effective therapies for treating melanoma.
Citation: T. L. Biechele, R. M. Kulikauskas, R. A. Toroni, O. M. Lucero, R. D. Swift, R. G. James, N. C. Robin, D. W. Dawson, R. T. Moon, A. J. Chien, Wnt/β-Catenin Signaling and AXIN1 Regulate Apoptosis Triggered by Inhibition of the Mutant Kinase BRAFV600E in Human Melanoma. Sci. Signal.5, ra3 (2012).
Allie H. Grossmann, Jae Hyuk Yoo, James Clancy, Lise K. Sorensen, Alanna Sedgwick, Zongzhong Tong, Kirill Ostanin, Aaron Rogers, Kenneth F. Grossmann, Sheryl R. Tripp, Kirk R. Thomas, Crislyn DSouza-Schorey, Shannon J. Odelberg, and Dean Y. Li (5 March 2013) Sci. Signal.6 (265), ra14.
[DOI: 10.1126/scisignal.2003398] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Friedegund Meier and Annalisa M. VanHook (29 January 2013) Sci. Signal.6 (260), pc3.
[DOI: 10.1126/scisignal.2003968] |Abstract »|Full Text »|Podcast »
Daniela Beck, Heike Niessner, Keiran S. M. Smalley, Keith Flaherty, Kim H. T. Paraiso, Christian Busch, Tobias Sinnberg, Sophie Vasseur, Juan Lucio Iovanna, Stefan Drießen, Björn Stork, Sebastian Wesselborg, Martin Schaller, Tilo Biedermann, Jürgen Bauer, Konstantinos Lasithiotakis, Benjamin Weide, Jürgen Eberle, Birgit Schittek, Dirk Schadendorf, Claus Garbe, Dagmar Kulms, and Friedegund Meier (29 January 2013) Sci. Signal.6 (260), ra7.
[DOI: 10.1126/scisignal.2003057] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Jordi Carreras Puigvert, Louise von Stechow, Ramakrishnaiah Siddappa, Alex Pines, Mahnoush Bahjat, Lizette C. J. M. Haazen, Jesper V. Olsen, Harry Vrieling, John H. N. Meerman, Leon H. F. Mullenders, Bob van de Water, and Erik H. J. Danen (22 January 2013) Sci. Signal.6 (259), ra5.
[DOI: 10.1126/scisignal.2003208] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Folkert Verkaar, Ken M. Cadigan, and Renée van Amerongen (11 December 2012) Sci. Signal.5 (254), mr2.
[DOI: 10.1126/scisignal.2003714] |Abstract »|Full Text »|PDF »