Detecting PKC phosphorylation as part of the Wnt/calcium pathway in cutaneous melanoma

Samudra K. Dissanayake, Ashani T. Weeraratna

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationWnt Signaling
Subtitle of host publicationPathway Methods and Mammalian Models
EditorsElizabeth Vincan
Pages157-172
Number of pages16
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume468
ISSN (Print)1064-3745

Keywords

  • Melanoma
  • PKC
  • Protein kinase C
  • Wnt5A

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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  • Cite this

    Dissanayake, S. K., & Weeraratna, A. T. (2008). Detecting PKC phosphorylation as part of the Wnt/calcium pathway in cutaneous melanoma. In E. Vincan (Ed.), Wnt Signaling: Pathway Methods and Mammalian Models (pp. 157-172). (Methods in Molecular Biology; Vol. 468). https://doi.org/10.1007/978-1-59745-249-6_12