title: Identifying and targeting determinants of melanoma cellular invasion.
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.
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.|Department of Medicine, University of Melbourne, Victoria, Australia.|School of Cancer Medicine, La Trobe University, Victoria, Australia.|The University of Queensland School of Medicine and the Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Queensland, Australia.
authors.forename: Aparna
authors.initials: A
authors.lastname: Jayachandran
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.|Department of Medicine, University of Melbourne, Victoria, Australia.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Prithviraj
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.
authors.forename: Pu-Han
authors.initials: PH
authors.lastname: Lo
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.
authors.forename: Marzena
authors.initials: M
authors.lastname: Walkiewicz
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.|Department of Medicine, University of Melbourne, Victoria, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Anaka
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, Australia.
authors.forename: Briannyn L
authors.initials: BL
authors.lastname: Woods
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.|Department of Medicine, University of Melbourne, Victoria, Australia.
authors.forename: BeeShin
authors.initials: B
authors.lastname: Tan
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.|Department of Medicine, University of Melbourne, Victoria, Australia.|School of Cancer Medicine, La Trobe University, Victoria, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Behren
authors.affiliation: Olivia Newton-John Cancer Research Institute, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia.|Ludwig Institute for Cancer Research, Melbourne-Austin Branch, Victoria, Australia.|Department of Medicine, University of Melbourne, Victoria, Australia.|School of Cancer Medicine, La Trobe University, Victoria, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria, Australia.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: McKeown
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002642:Chick Embryo; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056726:Genetic Association Studies; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000494:pharmacology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D059467:Transcriptome / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering
keywords: embryonic chicken transplantation; epithelial-to-mesenchymal transition; invasion; melanoma