Identification of glycogen synthase kinase 3α as a therapeutic target in melanoma.
In: Pigment Cell & Melanoma Research, Jg. 26 (2013-11-01), Heft 6, S. 886-900
Online
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Zugriff:
Deregulated expression or activity of kinases can lead to melanomas, but often the particular kinase isoform causing the effect is not well established, making identification and validation of different isoforms regulating disease development especially important. To accomplish this objective, an si RNA screen was undertaken that which identified glycogen synthase kinase 3α ( GSK3α) as an important melanoma growth regulator. Melanocytes and melanoma cell lines representing various stages of melanoma tumor progression expressed both GSK3α and GSK3β, but analysis of tumors in patients with melanoma showed elevated expression of GSK3α in 72% of samples, which was not observed for GSK3β. Furthermore, 80% of tumors in patients with melanoma expressed elevated levels of catalytically active phosphorylated GSK3α (p GSK3α Y279), but not phosphorylated GSK3β (p GSK3β Y216). si RNA-mediated reduction in GSK3α protein levels reduced melanoma cell survival and proliferation, sensitized cells to apoptosis-inducing agents and decreased xenografted tumor development by up to 56%. Mechanistically, inhibiting GSK3α expression using si RNA or the pharmacological agent AR- A014418 arrested melanoma cells in the G0/ G1 phase of the cell cycle and induced apoptotic death to retard tumorigenesis. Therefore, GSK3α is a key therapeutic target in melanoma. [ABSTRACT FROM AUTHOR]
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Titel: |
Identification of glycogen synthase kinase 3α as a therapeutic target in melanoma.
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Autor/in / Beteiligte Person: | Madhunapantula, Subba ; Rao, V. ; Sharma, Arati ; Gowda, Raghavendra ; Robertson, Gavin P. |
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Zeitschrift: | Pigment Cell & Melanoma Research, Jg. 26 (2013-11-01), Heft 6, S. 886-900 |
Veröffentlichung: | 2013 |
Medientyp: | academicJournal |
ISSN: | 1755-1471 (print) |
DOI: | 10.1111/pcmr.12156 |
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