Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40347-7 |
| _version_ | 1797452843065540608 |
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| author | Joanna Lazniewska Ka Lok Li Ian R. D. Johnson Alexandra Sorvina Jessica M. Logan Carmela Martini Courtney Moore Ben S.-Y. Ung Litsa Karageorgos Shane M. Hickey Sarita Prabhakaran Jessica K. Heatlie Robert D. Brooks Chelsea Huzzell Nicholas I. Warnock Mark P. Ward Bashir Mohammed Prerna Tewari Cara Martin Sharon O’Toole Laura Bogue Edgerton Mark Bates Paul Moretti Stuart M. Pitson Stavros Selemidis Lisa M. Butler John J. O’Leary Douglas A. Brooks |
| author_facet | Joanna Lazniewska Ka Lok Li Ian R. D. Johnson Alexandra Sorvina Jessica M. Logan Carmela Martini Courtney Moore Ben S.-Y. Ung Litsa Karageorgos Shane M. Hickey Sarita Prabhakaran Jessica K. Heatlie Robert D. Brooks Chelsea Huzzell Nicholas I. Warnock Mark P. Ward Bashir Mohammed Prerna Tewari Cara Martin Sharon O’Toole Laura Bogue Edgerton Mark Bates Paul Moretti Stuart M. Pitson Stavros Selemidis Lisa M. Butler John J. O’Leary Douglas A. Brooks |
| author_sort | Joanna Lazniewska |
| collection | DOAJ |
| description | 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 β3 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 β3 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. |
| first_indexed | 2024-03-09T15:14:31Z |
| format | Article |
| id | doaj.art-50253ef611194e4595e03d647adf9305 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:14:31Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-50253ef611194e4595e03d647adf93052023-11-26T13:09:55ZengNature PortfolioScientific Reports2045-23222023-08-0113111810.1038/s41598-023-40347-7Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progressionJoanna Lazniewska0Ka Lok Li1Ian R. D. Johnson2Alexandra Sorvina3Jessica M. Logan4Carmela Martini5Courtney Moore6Ben S.-Y. Ung7Litsa Karageorgos8Shane M. Hickey9Sarita Prabhakaran10Jessica K. Heatlie11Robert D. Brooks12Chelsea Huzzell13Nicholas I. Warnock14Mark P. Ward15Bashir Mohammed16Prerna Tewari17Cara Martin18Sharon O’Toole19Laura Bogue Edgerton20Mark Bates21Paul Moretti22Stuart M. Pitson23Stavros Selemidis24Lisa M. Butler25John J. O’Leary26Douglas A. Brooks27Clinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaClinical and Health Sciences, University of South AustraliaCentre for Cancer Biology, University of South Australia and SA PathologyDepartment of Histopathology, Trinity College DublinDepartment of Histopathology, Trinity College DublinDepartment of Histopathology, Trinity College DublinDepartment of Histopathology, Trinity College DublinDepartment of Histopathology, Trinity College DublinDepartment of Histopathology, Trinity College DublinDepartment of Histopathology, Trinity College DublinCentre for Cancer Biology, University of South Australia and SA PathologyCentre for Cancer Biology, University of South Australia and SA PathologySchool of Health and Biomedical Sciences, STEM College, RMIT UniversitySouth Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of AdelaideDepartment of Histopathology, Trinity College DublinClinical and Health Sciences, University of South AustraliaAbstract 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 β3 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 β3 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.https://doi.org/10.1038/s41598-023-40347-7 |
| spellingShingle | Joanna Lazniewska Ka Lok Li Ian R. D. Johnson Alexandra Sorvina Jessica M. Logan Carmela Martini Courtney Moore Ben S.-Y. Ung Litsa Karageorgos Shane M. Hickey Sarita Prabhakaran Jessica K. Heatlie Robert D. Brooks Chelsea Huzzell Nicholas I. Warnock Mark P. Ward Bashir Mohammed Prerna Tewari Cara Martin Sharon O’Toole Laura Bogue Edgerton Mark Bates Paul Moretti Stuart M. Pitson Stavros Selemidis Lisa M. Butler John J. O’Leary Douglas A. Brooks Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression Scientific Reports |
| title | Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression |
| title_full | Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression |
| title_fullStr | Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression |
| title_full_unstemmed | Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression |
| title_short | Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression |
| title_sort | dynamic interplay between sortilin and syndecan 1 contributes to prostate cancer progression |
| url | https://doi.org/10.1038/s41598-023-40347-7 |
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