Identifying and targeting determinants of melanoma cellular invasion
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Aparna Jayachandran1,2,3,4,5, Prashanth Prithviraj1,2,3, Pu-Han Lo2, Marzena Walkiewicz1,2, Matthew Anaka1,2,3, Briannyn L. Woods6, BeeShin Tan1,2,3, Andreas Behren1,2,3,4,*, Jonathan Cebon1,2,3,4,*, Sonja J. McKeown6,*
1Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia
2Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia
3Department of Medicine, University of Melbourne, Victoria, Australia
4School of Cancer Medicine, La Trobe University, Victoria, Australia
5The University of Queensland School of Medicine and the Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Queensland, Australia
6Department of Anatomy and Neuroscience, University of Melbourne, Victoria, Australia
*These authors contributed equally to this work
Sonja J. McKeown, email: firstname.lastname@example.org
Keywords: embryonic chicken transplantation, melanoma, epithelial-to-mesenchymal transition, invasion
Received: November 25, 2015 Accepted: April 22, 2016 Published: May 09, 2016
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.
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