High levels of transforming growth factor-β (TGFβ) correlate with poor prognosis for patients with prostate cancer and other cancers. TGFβ is a multifunctional cytokine and crucial regulator of cell fate, such as epithelial to mesenchymal transition (EMT), which is implicated in cancer invasion and progression. TGFβ conveys its signals upon binding to type I and type II serine/threonine kinase receptors (TβRI/II); phosphorylation of Smad2 and Smad3 promotes their association with Smad4, which regulates expression of targets genes, such as Smad7, p21, and c-Jun. TGFβ also activates the ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6), which associates with TβRI and activates the p38 mitogen-activated protein kinase (MAPK) pathway. Snail1 is a key transcription factor, induced by TGFβ that promotes migration and invasion of cancer cells. In this study, we have identified a novel binding site for c-Jun in the promoter of the Snail1 gene and report that the activation of the TGFβ-TRAF6-p38 MAPK pathway promotes both c-Jun expression and its activation via p38α-dependent phosphorylation of c-Jun at Ser63. The TRAF6-dependent activation of p38 also leads to increased stability of c-Jun, due to p38-dependent inactivation of glycogen synthase kinase (GSK) 3β by phosphorylation at Ser9. Thus, our findings elucidate a novel role for the p38 MAPK pathway in stimulated cells, leading to activation of c-Jun and its binding to the promoter of Snail1, thereby triggering motility and invasiveness of aggressive human prostate cancer cells.
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http://dx.doi.org/10.4161/cc.29339 | DOI Listing |
Urologie
January 2025
Klinik und Poliklinik für Urologie, Universitätsklinikum Essen, Hufelandstraße 55, 45147, Essen, Deutschland.
The superiority of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) over conventional staging methods such as computed tomography (CT) and bone scintigraphy has now been demonstrated for almost all clinical stages of prostate cancer. In primary diagnostics, PSMA-PET/CT is therefore the new standard for risk-adapted whole-body staging. At the same time, PSMA-PET/CT provides a new risk-based classification for predicting overall survival across all early and late stages of the disease.
View Article and Find Full Text PDFRadiol Artif Intell
January 2025
https://www.procancer-i.eu/.
Purpose To assess the impact of scanner manufacturer and scan protocol on the performance of deep learning models to classify prostate cancer (PCa) aggressiveness on biparametric MRI (bpMRI). Materials and Methods In this retrospective study, 5,478 cases from ProstateNet, a PCa bpMRI dataset with examinations from 13 centers, were used to develop five deep learning (DL) models to predict PCa aggressiveness with minimal lesion information and test how using data from different subgroups-scanner manufacturers and endorectal coil (ERC) use (Siemens, Philips, GE with and without ERC and the full dataset)-impacts model performance. Performance was assessed using the area under the receiver operating characteristic curve (AUC).
View Article and Find Full Text PDFHistol Histopathol
January 2025
Department of Cytology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Orchidectomy and estrogenization of the male represent a procedure that is applicable in sex reassignment or in prostate cancer therapy. This approach has an influence on the hypothalamic-pituitary-adrenal axis and thus affects cardiovascular function and metabolism. We utilized orchidectomized rats to evaluate the effects of estradiol on the structure and hormonal output of the adrenal gland.
View Article and Find Full Text PDFBJU Int
January 2025
Faculty of Social Sciences (Health Sciences), Prostate Cancer Research Center, Tampere University, Tampere, Finland.
Objective: To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy.
Patients And Methods: This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55-71 years randomised to the screening arm with PSA ≥4.
Mol Oncol
January 2025
Urologic Oncology Research Group, Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, Canada.
Patient stratification remains a challenge for optimal treatment of prostate cancer (PCa). This clinical heterogeneity implies intra-tumoural heterogeneity, with different prostate epithelial cell subtypes not all targeted by current treatments. We reported that such cell subtypes are traceable in liquid biopsies through representative transcripts.
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