Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line

Kalbe, Benjamin; Schulz, Viola M.; Schlimm, Marian; Philippou, Stathis; Jovancevic, Nikolina; Jansen, Fabian; Scholz, Paul; Lübbert, Hermann; Jarocki, Marvin; Faissner, Andréas; Hecker, Erich; Veitinger, Sophie; Tsai, Teresa; Osterloh, Sabrina; Hatt, Hanns

doi:10.1016/j.ejcb.2016.11.004

Cited by 53 publications

(61 citation statements)

References 38 publications

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“…Additionally, we observed an increased phosphorylation of AKT and of its substrate PRAS40 (Malla et al, 2015 ), which, in turn, verifies the AKT activation. An activation of protein kinases after odorant stimulation was shown in various studies (Busse et al, 2014 ; Maßberg et al, 2015 ; Kalbe et al, 2016d ; Weber et al, 2017 ). Kim et al were able to demonstrate that the AKT activation after stimulation with the OR10J5 agonist lyral depends on the receptor by the knockdown of OR10J5 in human umbilical vein endothelial cells (Kim et al, 2015 ).…”

Section: Discussionmentioning

confidence: 87%

Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

et al. 2017

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The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca2+-imaging experiments demonstrate that activation of OR51E2 triggers a Ca2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand β-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.

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Section: Discussionmentioning

confidence: 87%

Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

et al. 2017

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“…Additionally, the involvement of OR51E2 in prostate cancer development and progression was recently elucidated . ORs were also found to regulate the proliferation and apoptosis of cancer cells such as leukaemia and hepatocarcinoma cells . Recently, we demonstrated that the activation of OR51E2 induced pigmentation and differentiation and inhibited proliferation of human melanocytes …”

Section: Introductionmentioning

confidence: 99%

Functional expression of olfactory receptors in human primary melanoma and melanoma metastasis

Gelis

Jovancevic

Bechara

et al. 2017

Experimental Dermatology

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We identified the olfactory receptor 51E2 in human melanoma and have measured both OR51E2 mRNA and protein expression in melanoma tissue sections. qPCR analysis revealed that the receptor is upregulated in melanoma cells compared to normal melanocytes, indicating that OR51E2 may play a role in early melanoma development and progression. Activation of endogenous OR51E2 in cultured cells derived from metastatic and vertical-growth phase (VGP) by its ligand β-ionone results in an increase in the intracellular Ca concentration. RNAi experiments showed that the β-ionone-induced Ca signal depends on the activation of OR51E2. Furthermore, OR51E2 activation inhibits the growth of VGP melanoma cells via apoptotic processes. Cell motility assays revealed that treatment with β-ionone decreases the migration of VGP melanoma cells. Overall, our data demonstrates that OR51E2 is involved in the regulation of cell proliferation and migration, suggesting that it may serve as a novel target for melanoma therapy.

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“…In hepatocarcinoma cells, activation of OR1A2 by citronellal leads to calcium signals and a reduction in cell proliferation ( 15 ). In non-small-cell lung cancer, OR2J3 expression increases upon helional application, and furthermore, the activation induces apoptosis and inhibits cell proliferation ( 16 ). Melanoma cells express the receptor OR51E2, which is upregulated in these cells in comparison to normal melanocytes, indicating that OR51E2 might play a role in early melanoma development and progression ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Olfactory Receptors as Biomarkers in Human Breast Carcinoma Tissues

et al. 2018

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Olfactory receptors (ORs) are known to be expressed in a variety of human tissues and act on different physiological processes, such as cell migration, proliferation, or secretion and have been found to function as biomarkers for carcinoma tissues of prostate, lung, and small intestine. In this study, we analyzed the OR expression profiles of several different carcinoma tissues, with a focus on breast cancer. The expression of OR2B6 was detectable in breast carcinoma tissues; here, transcripts of OR2B6 were detected in 73% of all breast carcinoma cell lines and in over 80% of all of the breast carcinoma tissues analyzed. Interestingly, there was no expression of OR2B6 observed in healthy tissues. Immunohistochemical staining of OR2B6 in breast carcinoma tissues revealed a distinct staining pattern of carcinoma cells. Furthermore, we detected a fusion transcript containing part of the coding exon of OR2B6 as a part of a splice variant of the histone HIST1H2BO transcript. In addition, in cancer tissues and cell lines derived from lung, pancreas, and brain, OR expression patterns were compared to that of corresponding healthy tissues. The number of ORs detected in lung carcinoma tissues was significantly reduced in comparison to the surrounding healthy tissues. In pancreatic carcinoma tissues, OR4C6 was considerably more highly expressed in comparison to the respective healthy tissues. We detected OR2B6 as a potential biomarker for breast carcinoma tissues.

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Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line

Cited by 53 publications

References 38 publications

Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

Functional expression of olfactory receptors in human primary melanoma and melanoma metastasis

Olfactory Receptors as Biomarkers in Human Breast Carcinoma Tissues

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