Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/140155
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Type: | Journal article |
Title: | Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression |
Author: | Lazniewska, J. Li, K.L. Johnson, I.R.D. Sorvina, A. Logan, J.M. Martini, C. Moore, C. Ung, B.S.Y. Karageorgos, L. Hickey, S.M. Prabhakaran, S. Heatlie, J.K. Brooks, R.D. Huzzell, C. Warnock, N.I. Ward, M.P. Mohammed, B. Tewari, P. Martin, C. O’Toole, S. et al. |
Citation: | Scientific Reports, 2023; 13(1):1-18 |
Publisher: | Springer Science and Business Media LLC |
Issue Date: | 2023 |
ISSN: | 2045-2322 2045-2322 |
Statement of Responsibility: | Joanna Lazniewska ... Lisa M. Butler ... Robert D. Brooks ... Stuart M. Pitson ... et al. |
Abstract: | Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with β<sub>3</sub> integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly β<sub>3</sub> integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa. |
Keywords: | Androgen Antagonists Androgens Humans Integrin beta3 Male Neoplastic Processes Prostate Prostatic Neoplasms Syndecan-1 |
Rights: | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
DOI: | 10.1038/s41598-023-40347-7 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1092904 |
Published version: | http://dx.doi.org/10.1038/s41598-023-40347-7 |
Appears in Collections: | Medicine publications |
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File | Description | Size | Format | |
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hdl_140155.pdf | Published version | 14.07 MB | Adobe PDF | View/Open |
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