Abstract
Signaling networks play crucial roles in the changes leading to malignancy. In melanoma, increased Wnt5A expression increases melanoma cell motility via activation of protein kinase C (PKC). PKC isoforms comprise a family of serine/threonine kinases that are involved in the transduction of signals for cell proliferation, differentiation, and metastasis. The important role of PKC in processes leading to carcinogenesis and tumor cell invasion would render PKC a suitable target for cancer therapy, if not for its ubiquitous nature. Thus, targeting pathways leading to PKC activation that are more tumor specific, such as the non-canonical Wnt pathway, may prove to be the key to targeting PKC in cancer. Here we summarize the current understanding of the Wnt/calcium pathway and discuss methods of detecting activated/phos-phorylated PKC as a result of Wnt signaling in malignant melanoma. We have shown that overexpression of Wnt5A results in the activation of PKC, while inhibition of Wnt5A via small interfering RNA (siRNA) treatment results in its inactivation. In addition, the use of PKC activators and inhibitors has allowed us to study Wnt5A effects on downstream genes that may prove to be key targets for molecular therapy.
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Acknowledgments
We thank Dr. Arya Biragyn and Dr. Teresa D'Souza for helpful comments on this manuscript. Any data represented in this chapter was generated with the support of funds from the Intramural Research Program of the National Institute on Aging, Baltimore, MD.
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© 2008 Humana Press, a part of Springer Science+Business Media, LLC
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Dissanayake, S.K., Weeraratna, A.T. (2008). Detecting PKC Phosphorylation as Part of the Wnt/Calcium Pathway in Cutaneous Melanoma. In: Vincan, E. (eds) Wnt Signaling. Methods in Molecular Biology™, vol 468. Humana Press. https://doi.org/10.1007/978-1-59745-249-6_12
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DOI: https://doi.org/10.1007/978-1-59745-249-6_12
Publisher Name: Humana Press
Print ISBN: 978-1-58829-912-3
Online ISBN: 978-1-59745-249-6
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