Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.

Autor: Lazniewska J; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia. joanna.lazniewska@unisa.edu.au., Li KL; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Johnson IRD; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Sorvina A; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Logan JM; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Martini C; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Moore C; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Ung BS; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Karageorgos L; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Hickey SM; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Prabhakaran S; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia.; Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia., Heatlie JK; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Brooks RD; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Huzzell C; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Warnock NI; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, 5000, Australia., Ward MP; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Mohammed B; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Tewari P; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Martin C; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., O'Toole S; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Edgerton LB; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Bates M; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Moretti P; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, 5000, Australia., Pitson SM; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, 5000, Australia., Selemidis S; School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, VIC, 3083, Australia., Butler LM; South Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, 5000, Australia.; Solid Tumour Program, Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia., O'Leary JJ; Department of Histopathology, Trinity College Dublin, Dublin 8, Ireland., Brooks DA; Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia. doug.brooks@unisa.edu.au.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Aug 18; Vol. 13 (1), pp. 13489. Date of Electronic Publication: 2023 Aug 18.
DOI: 10.1038/s41598-023-40347-7
Abstrakt: 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 3 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 3 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje