FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379160599> ?p ?o ?g. }

• W4379160599 endingPage "A024" @default.
• W4379160599 startingPage "A024" @default.
• W4379160599 abstract "Abstract Lethal prostate cancer (PCa) is characterized by the presence of metastases and the development of resistance to therapies. Metastases form in a multi-step process enabled by dynamic cytoskeleton remodeling. An actin cytoskeleton regulating gene, CALD1, encodes a protein caldesmon (CaD). Its isoform, low-molecular-weight CaD (l-CaD), operates in non-muscle cells, supporting the function of filaments involved in force production and mechanosensing. Several factors, including glucocorticoid receptor (GR), have been identified as regulators of l-CaD in different cell types, but the regulation of l-CaD in PCa has not been defined. PCa develops resistance in response to therapeutic inhibition of androgen signaling by multiple strategies. Known strategies include androgen receptor (AR) alterations, modified steroid synthesis, and bypassing AR signaling, for example, by GR upregulation. The goal of our study was to characterize the potential role of l-CaD in PCa metastases and antiandrogen therapy resistance. In this study, we extracted co-expression data of l-CaD from the largest public PCa patient data sets and identified the common transcripts between the sets. The common co-expression hits were used to recognize biological processes associated with l-CaD in the PCa context. Next, we used in vitro techniques, including 3D culture, cell viability assays, immunofluorescence staining, and Western blotting, to study the role of l-CaD in PCa with a focus on cancer hallmarks and the recognized associated biological processes. Finally, we used in vivo zebrafish and mouse xenograft models to verify the findings observed in silico in PCa patient data and in vitro in PC3, DU145, and VCaP cell lines. Here, we report that in vitro downregulation of l-CaD promotes the epithelial phenotype and reduces the spheroid growth in 3D, which is reflected in vivo in the reduced formation of metastases in a zebrafish PCa xenograft model. In accordance, CALD1 mRNA expression correlates with epithelial-to-mesenchymal transition transcripts in PCa patients. We also show that CALD1 is highly co-expressed with GR in multiple PCa data sets and that GR activation upregulates l-CaD in vitro. Moreover, GR upregulation associates with increased l-CaD expression after the development of resistance to antiandrogen therapy in PCa xenograft mouse models. In summary, GR-regulated l-CaD plays a role in forming PCa metastases, being clinically relevant when antiandrogen resistance is attained by the means of bypassing AR signaling by GR upregulation. Citation Format: Verneri Virtanen, Kreetta Paunu, Antti Kukkula, Saana Niva, Ylva Junila, Mervi Toriseva, Terhi Jokilehto, Sari Mäkelä, Riikka Huhtaniemi, Matti Poutanen, Ilkka Paatero, Maria Sundvall. Glucocorticoid receptor-induced non-muscle caldesmon regulates growth and metastasis in castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A024." @default.
• W4379160599 created "2023-06-03" @default.
• W4379160599 creator A5001485426 @default.
• W4379160599 creator A5010661573 @default.
• W4379160599 creator A5014782116 @default.
• W4379160599 creator A5015741341 @default.
• W4379160599 creator A5025781737 @default.
• W4379160599 creator A5045196506 @default.
• W4379160599 creator A5064220321 @default.
• W4379160599 creator A5069911296 @default.
• W4379160599 creator A5073300793 @default.
• W4379160599 creator A5077800239 @default.
• W4379160599 creator A5080251712 @default.
• W4379160599 creator A5080497006 @default.
• W4379160599 date "2023-06-02" @default.
• W4379160599 modified "2023-10-13" @default.
• W4379160599 title "Abstract A024: Glucocorticoid receptor-induced non-muscle caldesmon regulates growth and metastasis in castration-resistant prostate cancer" @default.
• W4379160599 doi "https://doi.org/10.1158/1538-7445.prca2023-a024" @default.
• W4379160599 hasPublicationYear "2023" @default.
• W4379160599 type Work @default.
• W4379160599 citedByCount "0" @default.
• W4379160599 crossrefType "journal-article" @default.
• W4379160599 hasAuthorship W4379160599A5001485426 @default.
• W4379160599 hasAuthorship W4379160599A5010661573 @default.
• W4379160599 hasAuthorship W4379160599A5014782116 @default.
• W4379160599 hasAuthorship W4379160599A5015741341 @default.
• W4379160599 hasAuthorship W4379160599A5025781737 @default.
• W4379160599 hasAuthorship W4379160599A5045196506 @default.
• W4379160599 hasAuthorship W4379160599A5064220321 @default.
• W4379160599 hasAuthorship W4379160599A5069911296 @default.
• W4379160599 hasAuthorship W4379160599A5073300793 @default.
• W4379160599 hasAuthorship W4379160599A5077800239 @default.
• W4379160599 hasAuthorship W4379160599A5080251712 @default.
• W4379160599 hasAuthorship W4379160599A5080497006 @default.
• W4379160599 hasConcept C121608353 @default.
• W4379160599 hasConcept C134018914 @default.
• W4379160599 hasConcept C2779013556 @default.
• W4379160599 hasConcept C2780192828 @default.
• W4379160599 hasConcept C2780841215 @default.
• W4379160599 hasConcept C502942594 @default.
• W4379160599 hasConcept C54355233 @default.
• W4379160599 hasConcept C59493245 @default.
• W4379160599 hasConcept C61367390 @default.
• W4379160599 hasConcept C86803240 @default.
• W4379160599 hasConceptScore W4379160599C121608353 @default.
• W4379160599 hasConceptScore W4379160599C134018914 @default.
• W4379160599 hasConceptScore W4379160599C2779013556 @default.
• W4379160599 hasConceptScore W4379160599C2780192828 @default.
• W4379160599 hasConceptScore W4379160599C2780841215 @default.
• W4379160599 hasConceptScore W4379160599C502942594 @default.
• W4379160599 hasConceptScore W4379160599C54355233 @default.
• W4379160599 hasConceptScore W4379160599C59493245 @default.
• W4379160599 hasConceptScore W4379160599C61367390 @default.
• W4379160599 hasConceptScore W4379160599C86803240 @default.
• W4379160599 hasIssue "11_Supplement" @default.
• W4379160599 hasLocation W43791605991 @default.
• W4379160599 hasOpenAccess W4379160599 @default.
• W4379160599 hasPrimaryLocation W43791605991 @default.
• W4379160599 hasRelatedWork W1543920337 @default.
• W4379160599 hasRelatedWork W2015889618 @default.
• W4379160599 hasRelatedWork W2082788526 @default.
• W4379160599 hasRelatedWork W2735781373 @default.
• W4379160599 hasRelatedWork W2772229485 @default.
• W4379160599 hasRelatedWork W2806156214 @default.
• W4379160599 hasRelatedWork W2808221505 @default.
• W4379160599 hasRelatedWork W2927728931 @default.
• W4379160599 hasRelatedWork W4361849260 @default.
• W4379160599 hasRelatedWork W4361849348 @default.
• W4379160599 hasVolume "83" @default.
• W4379160599 isParatext "false" @default.
• W4379160599 isRetracted "false" @default.
• W4379160599 workType "article" @default.