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Identifying and targeting determinants of melanoma cellular invasion

2016; Impact Journals LLC; Volume: 7; Issue: 27 Linguagem: Inglês

10.18632/oncotarget.9227

1949-2553

Aparna Jayachandran, Prashanth Prithviraj, Pu‐Han Lo, Marzena Walkiewicz, Matthew Anaka, Briannyn Woods, BeeShin Tan, Andreas Behren, Jonathan Cebon, Sonja J. McKeown,

RNA Interference and Gene Delivery

// Aparna Jayachandran 1, 2, 3, 4, 5 , Prashanth Prithviraj 1, 2, 3 , Pu-Han Lo 2 , Marzena Walkiewicz 1, 2 , Matthew Anaka 1, 2, 3 , Briannyn L. Woods 6 , BeeShin Tan 1, 2, 3 , Andreas Behren 1, 2, 3, 4, * , Jonathan Cebon 1, 2, 3, 4, * , Sonja J. McKeown 6, * 1 Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia 2 Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia 3 Department of Medicine, University of Melbourne, Victoria, Australia 4 School of Cancer Medicine, La Trobe University, Victoria, Australia 5 The University of Queensland School of Medicine and the Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Queensland, Australia 6 Department of Anatomy and Neuroscience, University of Melbourne, Victoria, Australia * These authors contributed equally to this work Correspondence to: Sonja J. McKeown, email: s.mckeown@unimelb.edu.au Keywords: embryonic chicken transplantation, melanoma, epithelial-to-mesenchymal transition, invasion Received: November 25, 2015 Accepted: April 22, 2016 Published: May 09, 2016 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.