La Trobe

Identifying and targeting determinants of melanoma cellular invasion

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posted on 2023-02-23, 04:02 authored by A Jayachandran, P Prithviraj, P-H Lo, M Walkiewicz, M Anaka, BL Woods, B Tan, Andreas BehrenAndreas Behren, Jonathan Cebon, SJ McKeown
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.

Funding

We would like to acknowledge the Melanoma Research Alliance (MRA) and the Melbourne Melanoma Project (MMP) for partial funding of this project. The Olivia Newton-John Cancer Research Institute acknowledges the part support of Ludwig Cancer Research and the Operational Infrastructure Support Program of the Victorian State GOVernment. AJ was supported by Cure Cancer Australia Foundation with the support of Cancer Australia and Austin Medical Research Foundation. AB was supported by Cure Cancer Australia Foundation project grant. SJM was supported by a University of Melbourne Early Career Fellowship. The establishment of an expression profile in melanoma cell lines was funded by a grant from the Austin Medical Research Foundation to AB.

History

Publication Date

2016-05-09

Journal

Oncotarget

Volume

7

Issue

27

Pagination

17p. (p. 41186-41202)

Publisher

Impact Journals

ISSN

1949-2553

Rights Statement

© 2016 The Authors. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. Under the CC BY, authors retain ownership of the copyright for their article, but authors allow anyone to download, reuse, reprint, modify, distribute, and/or copy the article, so long as the original authors and source are cited. No permission is required from the authors or the publishers. For queries about the license, please contact us at forms@oncotarget.com

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