Identifying and targeting determinants of melanoma cellular invasion

Aparna Jayachandran, Prashanth Prithviraj, Pu-Han Lo, Marzena Walkiewicz, Matthew Anaka, Briannyn L. Woods, Bee Shin Tan, Andreas Behren, Jonathon Cebon, Sonja J. McKeown

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

Epithelial-to-mesenchymal transition is a critical process that increases the malignant potential of melanoma by facilitating invasion and dissemination of tumor cells. This study identified genes involved in the regulation of cellular invasion and evaluated whether they can be targeted to inhibit melanoma invasion. We identified Peroxidasin (PXDN), Netrin 4 (NTN4) and GLIS Family Zinc Finger 3 (GLIS3) genes consistently elevated in invasive mesenchymal-like melanoma cells. These genes and proteins were highly expressed in metastatic melanoma tumors, and gene silencing led to reduced melanoma invasion in vitro. Furthermore, migration of PXDN, NTN4 or GLIS3 siRNA transfected melanoma cells was inhibited following transplantation into the embryonic chicken neural tube compared to control siRNA transfected melanoma cells. Our study suggests that PXDN, NTN4 and GLIS3 play a functional role in promoting melanoma cellular invasion, and therapeutic approaches directed toward inhibiting the action of these proteins may reduce the incidence or progression of metastasis in melanoma patients.
Original languageEnglish
Pages (from-to)41186-41202
Number of pages17
JournalOncotarget
Volume7
Issue number27
DOIs
Publication statusPublished - 9 May 2016
Externally publishedYes

Keywords

  • embryonic chicken transplantation
  • melanoma
  • epithelial-to-mesenchymal transition
  • invasion

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