Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Martini, Carmela; Logan, Jessica M.; Sorvina, Alexandra; Gordon, Colin; Beck, Andrew R.; Ung, Ben S.-Y.; Caruso, Maria C.; Moore, Courtney; Hocking, Ashleigh; Johnson, I. R.; Li, Ka Lok; Karageorgos, Litsa; Hopkins, Ashley M.; Esterman, Adrian; Huzzell, Chelsea; Brooks, Robert D.; Łaźniewska, Joanna; Hickey, Shane M.; Bader, Christie A.; Parkinson-Lawrence, Emma J.; Weigert, Roberto; Sorich, Michael J.; Tewari, Prerna; Martin, Cara; O’Toole, Sharon; Bates, Mark; Ward, Mark P.; Mohammed, Bashir; Keegan, Helen; Watson, R. William G.; Sophie, Prendergast,; Heffernan, Sheena; NiMhaolcatha, Sarah; O’Connor, Roisin M.; Malone, Victoria; Carter, Marguerite; Ryan, Katie Beth; Brady, Nathan R.; Clarke, Andres; Sokol, Filip; Prabhakaran, Sarita; Stahl, Jürgen; Klebe, Sonja; Samaratunga, Hemamali; Delahunt, Brett; Selemidis, Stavros; Moretti, Kim; Butler, Lisa M.; O’Leary, John; Brooks, Douglas A.

doi:10.1016/j.pathol.2022.08.001

Cited by 17 publications

(27 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The differential detection of sortilin and syndecan-1 in well-and poorly-formed malignant glands aligns respectively with low-and high-grades of PCa 12 , suggesting that these proteins are central to PCa pathogenesis and disease progression. We hypothesised that the high expression of sortilin in low-grade PCa aligns with the regulation of glucose metabolism in androgen-sensitive cells (LNCaP), while elevated syndecan-1 expression in high-grade PCa aligns with lipid metabolism in androgen-insensitive cells (PC3).…”

Section: Introductionmentioning

confidence: 78%

“…1b). These immunolabelling patterns were representative of a large cohort of tissue samples from PCa patients (n > 100), which were previously used to validate these markers 12 .…”

Section: Resultsmentioning

confidence: 99%

“…We showed that increasing glucose concentration decreased sortilin but increased GLUT1 expression in LNCaP cells, suggesting that in in androgen-responsive cells there is a glucose concentration-related link between sortilin and GLUT1 expression. We recently discovered that sortilin is overexpressed in low-grade PCa, but has a low level of expression in benign tissue and high-grade cancer 12 . Accordingly, we showed that sortilin was most abundant in LNCaP cells, when compared to PNT2 and PC3 cells; and similar expression patterns were observed for GLUT1 and GLUT4.…”

Section: Discussionmentioning

confidence: 99%

“…Endosomes and lysosomes have a critical role in cellular uptake, intracellular tra cking/cargo sorting, signalling, in ammation, and metabolism, which are all hallmarks of PCa pathogenesis 9 . We have previously reported altered regulation of the endosome-lysosome system in PCa 10,11 and more recently demonstrated that sortilin and syndecan-1 delineate PCa pathogenesis in patient tissues 12 . Sortilin and syndecan-1 have been implicated in the development and progression of many malignancies, including PCa 13,14 .…”

Section: Introductionmentioning

confidence: 92%

“…Heat induced epitope retrieval was carried out in Tris-EDTA Buffer (10 mM Tris Base, 1 mM EDTA Solution, 0.05% Tween®-20, pH 9.0) in a Sharp model R-9270 microwave oven heated on high for 4 min and medium-low for a further 15 min. Tissue sections underwent endogenous peroxidase blocking with 3% H 2 O 2 for 5 mins before incubation with 200 µl of primary antibody for 1 h at room temperature (RT) (sortillin; 0.273 µg/ml, syndecan-1; 2.958 µg/ml) 12 . Immunolabelling detection was performed using the DAKO EnVision + and Liquid diaminobenzidine (DAB) + System kits (Dako Australia Pty Ltd., NSW, Australia) as per manufacturer's instructions.…”

Section: Histology and Immunohistochemistry (Ihc)mentioning

confidence: 99%

See 4 more Smart Citations

Dynamic interplay between sortilin and syndecan-1 drives a metabolic switch during prostate cancer progression

Łaźniewska

Johnson

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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 (selected to match the biomarker phenotypes in tissue from PCa patients) 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 has significance for disease progression and how androgen-deprivation therapy may promote castration-resistant PCa.

show abstract

Section: Introductionmentioning

confidence: 78%

“…1b). These immunolabelling patterns were representative of a large cohort of tissue samples from PCa patients (n > 100), which were previously used to validate these markers 12 .…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Histology and Immunohistochemistry (Ihc)mentioning

confidence: 99%

See 3 more Smart Citations

Dynamic interplay between sortilin and syndecan-1 drives a metabolic switch during prostate cancer progression

Łaźniewska

Johnson

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Distinct patterns of biomarker expression for atypical intraductal proliferations in prostate cancer

Martini,

Logan,

Sorvina

et al. 2023

Virchows Arch

View full text Add to dashboard Cite

High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations. Tissue samples from 86 patients with prostate cancer were assessed by routine haematoxylin and eosin staining and immunohistochemistry (IHC) with a biomarker panel (Appl1/Sortilin/Syndecan-1) and a PIN4 cocktail (34βE12+P63/P504S). Appl1 strongly labelled atypical secretory cells, effectively visualising intraductal lesions. Sortilin labelling was moderate-to-strong in > 70% of cases, while Syndecan-1 was moderate-to-strong in micropapillary HGPIN/AIP lesions (83% cases) versus flat/tufting HGPIN (≤ 20% cases). Distinct biomarker labelling patterns for atypical intraductal lesions of the prostate were observed, including early atypical changes (flat/tufting HGPIN) and more advanced atypical changes (micropapillary HGPIN/AIP). Furthermore, the biomarker panel may be used as a tool to overcome the diagnostic uncertainty surrounding AIP by supporting a definitive diagnosis of IDCP for such lesions displaying the same biomarker pattern as cribriform IDCP.

show abstract

Exploring the role of sporadic BRAF and KRAS mutations during colorectal cancer pathogenesis: A spotlight on the contribution of the endosome-lysosome system

Tang,

Lam,

Brooks

et al. 2024

Cancer Letters

View full text Add to dashboard Cite

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Cited by 17 publications

References 46 publications

Dynamic interplay between sortilin and syndecan-1 drives a metabolic switch during prostate cancer progression

Dynamic interplay between sortilin and syndecan-1 drives a metabolic switch during prostate cancer progression

Distinct patterns of biomarker expression for atypical intraductal proliferations in prostate cancer

Exploring the role of sporadic BRAF and KRAS mutations during colorectal cancer pathogenesis: A spotlight on the contribution of the endosome-lysosome system

Contact Info

Product

Resources

About