Functional characterization of the ectopically expressed olfactory receptor 2AT4 in human myelogenous leukemia

Manteniotis, Stavros; Wojcik, Sebastian; Brauhoff, P; Möllmann, Michael; Petersen, Lars C.; Göthert, Joachim R.; Schmiegel, Wolff; Dührsen, Ulrich; Gisselmann, Günter; Hatt, Hanns

doi:10.1038/cddiscovery.2015.70

Cited by 64 publications

(72 citation statements)

References 48 publications

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“…Despite our current data demonstrating an oncogenic function for ORs, several studies have suggested that ORs may act as tumour suppressors24565758. The activation of OR2AT4 and OR51B5 in myelogenous leukaemia K562 cells, decreased proliferation and enhanced apoptosis and differentiation5657.…”

Section: Discussioncontrasting

confidence: 55%

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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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Section: Discussioncontrasting

confidence: 55%

“…The activation of OR2AT4 and OR51B5 in myelogenous leukaemia K562 cells, decreased proliferation and enhanced apoptosis and differentiation5657. In addition, activation of OR51E1 in prostate cancer cells suppressed cell proliferation2458.…”

Section: Discussionmentioning

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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“…These findings have served as a basis for functional studies that demonstrate the potential of the ORs as drug targets (Neuhaus et al, 2009; Busse et al, 2014; Maßberg et al, 2015; Manteniotis et al, 2016a,b; Tsai et al, 2016). In this study, for the first time, we describe the expression of the OR mRNAs and the localization of the OR proteins in the mature human retina.…”

Section: Discussionmentioning

confidence: 96%

“…OR2AT4 is another example of the therapeutic potential of ORs in human skin because its activation promotes wound healing processes in human keratinocytes (Busse et al, 2014). They are also of major importance for the regulation of apoptosis, cytokinesis, hormone secretion and differentiation (Braun et al, 2007; Zhang et al, 2012; Maßberg et al, 2015; Gelis et al, 2016; Manteniotis et al, 2016a,b; Massberg et al, 2016; Tsai et al, 2016). However, the expression and localization of ORs in different areas of the brain, the spinal cord, the trigeminal (TG) and dorsal root ganglia (DRG) were recently described (Otaki et al, 2004; Garcia-Esparcia et al, 2013; Flegel et al, 2015; Goncalves et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors

Jovancevic

Wunderlich

Haering

et al. 2017

Front. Cell. Neurosci.

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Several studies have demonstrated that the expression of odorant receptors (ORs) occurs in various tissues. These findings have served as a basis for functional studies that demonstrate the potential of ORs as drug targets for a clinical application. To the best of our knowledge, this report describes the first evaluation of the mRNA expression of ORs and the localization of OR proteins in the human retina that set a stage for subsequent functional analyses. RNA-Sequencing datasets of three individual neural retinae were generated using Next-generation sequencing and were compared to previously published but reanalyzed datasets of the peripheral and the macular human retina and to reference tissues. The protein localization of several ORs was investigated by immunohistochemistry. The transcriptome analyses detected an average of 14 OR transcripts in the neural retina, of which OR6B3 is one of the most highly expressed ORs. Immunohistochemical stainings of retina sections localized OR2W3 to the photosensitive outer segment membranes of cones, whereas OR6B3 was found in various cell types. OR5P3 and OR10AD1 were detected at the base of the photoreceptor connecting cilium, and OR10AD1 was also localized to the nuclear envelope of all of the nuclei of the retina. The cell type-specific expression of the ORs in the retina suggests that there are unique biological functions for those receptors.

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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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Functional characterization of the ectopically expressed olfactory receptor 2AT4 in human myelogenous leukemia

Cited by 64 publications

References 48 publications

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

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

Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors

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

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