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http://purl.uniprot.org/citations/31760076http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31760076http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Recent studies have shown that 20-hydroxyeicosatetraenoic acid (20-HETE) is a key molecule in sustaining androgen-mediated prostate cancer cell survival. Thus, the aim of this study was to determine whether 20-HETE can affect the metastatic potential of androgen-insensitive prostate cancer cells, and the implication of the newly described 20-HETE receptor, GPR75, in mediating these effects.

Methods

The expression of GPR75, protein phosphorylation, actin polymerization and protein distribution were assessed by western blot and/or fluorescence microscopy. Additionally, in vitro assays including epithelial-mesenchymal transition (EMT), metalloproteinase-2 (MMP-2) activity, scratch wound healing, transwell invasion and soft agar colony formation were used to evaluate the effects of 20-HETE agonists/antagonists or GPR75 gene silencing on the aggressive features of PC-3 cells.

Results

20-HETE (0.1 nM) promoted the acquisition of a mesenchymal phenotype by increasing EMT, the release of MMP-2, cell migration and invasion, actin stress fiber formation and anchorage-independent growth. Also, 20-HETE augmented the expression of HIC-5, the phosphorylation of EGFR, NF-κB, AKT and p-38 and the intracellular redistribution of p-AKT and PKCα. These effects were impaired by GPR75 antagonism and/or silencing. Accordingly, the inhibition of 20-HETE formation with N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) elicited the opposite effects.

Conclusions

The present results show for the first time the involvement of the 20-HETE-GPR75 receptor in the activation of intracellular signaling known to be stimulated in cell malignant transformations leading to the differentiation of PC-3 cells towards a more aggressive phenotype. Targeting the 20-HETE/GPR75 pathway is a promising and novel approach to interfere with prostate tumor cell malignant progression."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.org/dc/terms/identifier"doi:10.1016/j.bbalip.2019.158573"xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Falck J.R."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Costas M.A."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Nowicki S."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Cardenas S."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Panelo L."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Colombero C."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/author"Dakarapu R."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/name"Biochim Biophys Acta Mol Cell Biol Lipids"xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/pages"158573"xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/title"GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells."xsd:string
http://purl.uniprot.org/citations/31760076http://purl.uniprot.org/core/volume"1865"xsd:string
http://purl.uniprot.org/citations/31760076http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31760076
http://purl.uniprot.org/citations/31760076http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31760076
http://purl.uniprot.org/uniprot/#_O95800-mappedCitation-31760076http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31760076
http://purl.uniprot.org/uniprot/O95800http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/31760076