PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB

Rodriguez, Melissa; Luo, Wen; Weng, Jian; Zeng, Li; Yi, Zhengfang; Siwko, Stefan; Liu, M.

doi:10.1038/oncsis.2014.29

Cited by 49 publications

(51 citation statements)

References 40 publications

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“…Recently, ORs came into the focus of drug development because ectopically expressed ORs were involved in physiological and pathophysiological mechanisms within human tissues, such as the chemotaxis of sperm, the proliferation of prostate cancer and liver cancer cells, the induction of wound-healing, the modulation of hepatic triglyceride metabolism, cytokinesis, apoptosis and the regulation of serotonin secretion [8, 13, 58, 60, 67, 79, 82, 90, 99, 108, 114]. …”

Section: Introductionmentioning

confidence: 99%

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

et al. 2017

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Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-017-0600-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

et al. 2017

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“…The β-ionone-dependent activation of OR51E2 resulted in a reduced proliferation of PCa cells via the Src-Pyk2- p38MAPK signaling pathway [45, 47, 48]. Controversy studies demonstrated prostate cancer growth promoting function of PSGR in vivo [49, 50]. Concomitantly, β-ionone stimulation even promotes LNCaP cell invasiveness in vitro and metastases spreading in vivo [49].…”

Section: Introductionmentioning

confidence: 99%

The activation of OR51E1 causes growth suppression of human prostate cancer cells

et al. 2016

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The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis.

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“…OR10J5 is expressed in the heart and is involved in angiogenesis27. Additionally, overexpressed OR51E2 (PSGR, prostate-specific G-protein-coupled receptor) enhanced oncogenesis in prostate tissue through activation of NF-κB28. However, the physiological roles of ORs in these tissues are still not well understood.…”

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confidence: 99%

Regulatory role of G9a and LSD1 in the Transcription of Olfactory Receptors during Leukaemia Cell Differentiation

Jung

Chae

Kim

et al. 2017

Sci Rep

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Recent studies have reported the ectopic expression of olfactory receptors (ORs) in non-olfactory tissues, however, their physiological roles were not well elucidated. ORs are expressed in and function in different types of cancers. Here, we identified that the H3K9me2 levels of several OR promoters decreased during differentiation in the HL-60, human myeloid leukaemia cell line, by all-trans-retinoic acid (ATRA). We found that the differential OR promoters H3K9me2 levels were regulated by G9a and LSD1, resulting in the decrease of ORs transcription during HL-60 differentiation. G9a and LSD1 could regulate the expression of ORs in several non-olfactory cells via the methylation and demethylation of H3K9me2. In addition, we demonstrated that knockdown of OR significantly reduced cell proliferation. Therefore, the epigenetic regulation of ORs transcription is critical for carcinogenesis.

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PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-κB

Cited by 49 publications

References 40 publications

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

The activation of OR51E1 causes growth suppression of human prostate cancer cells

Regulatory role of G9a and LSD1 in the Transcription of Olfactory Receptors during Leukaemia Cell Differentiation

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