Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

Tong, Teng; Wang, Yanan; Kang, Seong‐Gook; Huang, Kunlun

doi:10.3390/pharmaceutics13081314

Cited by 31 publications

(20 citation statements)

References 165 publications

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“…Ectopic olfactory receptors have diverse functions in different organs and tissues [3,26,27]. Genital organs are exposed to odorants constantly; thus, ectopic olfactory receptors may regulate intracellular signaling pathways and related physiologic functions in these organs.…”

Section: Discussionmentioning

confidence: 99%

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

Kim¹,

Dziobaka

Yoon³

et al. 2022

Preprint

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Background Olfactory receptors are expressed in multiple extra-nasal tissues and these ectopic olfactory receptors mediate tissue specific functions and regulate cellular physiology. Ectopic olfactory receptors may play key roles in tissues constantly exposed to odorants, thus functionality of these receptors in genital tissues are of particular interest. The functionality of ectopic olfactory receptors expressed in VK2/E6E7 human vaginal epithelial cells was investigated. Results OR2H2 was functionally expressed in VK2/E6E7 cells and activation of OR2H2 by aldehyde 13–13, a ligand of OR2H2, increased the intracellular calcium and cAMP concentrations. Immunoblotting demonstrated that activation of OR2H2 by aldehyde 13–13 stimulated the CAMKKβ-AMPK-mTOR-autophagy signaling axis, and that these effects were negated by OR2H2 knockdown. Autophagy activation suppressed aging and cellular senescence. Activation of OR2H2 by aldehyde 13–13 restored proliferation, reduced the expression of senescence markers, P16 and P19 in H2O2-induced senescent cells. Additionally, aldehyde 13–13 showed senolytic activity by predominantly inducing apoptosis of H2O2-induced senescent cells compared with non-senescent normal cells. In vivo, aldehyde 13–13 increased the lifespan of Caenorhabditis elegans and budding yeast. Conclusions These findings demonstrate that OR2H2 is a functional receptor in VK2/E6E7 cells and activation of OR2H2 activates AMPK-autophagy axis, suppresses cellular aging and senescence, thus may increase cellular lifespan.

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Section: Discussionmentioning

confidence: 99%

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

Kim¹,

Dziobaka

Yoon³

et al. 2022

Preprint

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show abstract

“…Overall, this suggests that the aberrant expression of ORs might contribute to the cancer phenotype. In cancer cells, ORs act as chemoreceptors 52 . In comparison to healthy prostate tissue, prostate cancer shows a high tumor‐specific overexpression (i.e., more than 10‐fold) of OR51E1 and OR51E2 in two‐thirds of cases (Table 1) (Figure 1).…”

Section: Olfactory Receptorsmentioning

confidence: 99%

“…In cancer cells, ORs act as chemoreceptors. 52 In comparison to healthy prostate tissue, prostate cancer shows a high tumor-specific overexpression (i.e., more than 10-fold) of OR51E1 and OR51E2 in two-thirds of cases (Table 1) (Figure 1). The full spectrum of their ligands is still unknown, but deorphanization efforts showed that they can be activated by lactate, butyric acid, propionic acid, and other aliphatic acids.…”

Section: Introductionmentioning

confidence: 99%

Orphan receptors in prostate cancer

Sakellakis

2022

The Prostate

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Background: The identification of new cellular receptors has been increasing rapidly.A receptor is called "orphan" if an endogenous ligand has not been identified yet.Methods: Here we review receptors that contribute to prostate cancer and are considered orphan or partially orphan. This means that the full spectrum of their endogenous ligands remains unknown. Results:The orphan receptors are divided into two major families. The first group includes G protein-coupled receptors. Most are orphan olfactory receptors. OR51E1 inhibits cell proliferation and induces senescence in prostate cancer. OR51E2 inhibits prostate cancer growth, but promotes invasiveness and metastasis. GPR158, GPR110, and GPCR-X play significant roles in prostate cancer development and progression. However, GPR160 induces cell cycle arrest and apoptosis.The other major subset of orphan receptors are nuclear receptors. Receptor-related orphan receptor α (RORα) inhibits tumor growth, but RORγ stimulates androgen receptor signaling. PXR contributes to metabolic deactivation of androgens and inhibits cell proliferation. TLX has protumorigenic effects in prostate cancer, while its knockdown triggers cellular senescence and growth arrest. Estrogen-related receptor ERRγ can inhibit tumor growth but ERRα is protumorigenic. Dax1 and short heterodimeric partner are also inhibitory in prostate cancer. Conclusion:There is a "zoo" of relatively underappreciated orphan receptors that play key roles in prostate cancer.

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“…Overall, this suggests that the aberrant expression of ORs might contribute to the cancer phenotype. In cancer cells, ORs act as chemoreceptors 33 . In comparison to healthy prostate tissue, prostate cancer shows a high tumor-specific overexpression (i.e., more than 10fold) of OR51E1 and OR51E2 in two-third of cases 34 .…”

Section: Olfactory Receptorsmentioning

confidence: 99%

Orphan Receptors in Prostate Cancer

Sakellakis¹

2022

Preprint

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Background: The identification of new cellular receptors has been increasing rapidly. A receptor is called “orphan” if an endogenous ligand has not been identified yet. Methods: Here we review receptors that contribute to prostate cancer and are considered orphan or partially orphan. This means that the full spectrum of their endogenous ligands remains unknown. Results: The orphan receptors are divided into two major families. The first group includes G protein-coupled receptors. Most are orphan olfactory receptors. OR51E1 inhibits cell proliferation and induces senescence in prostate cancer. OR51E2 inhibits prostate cancer growth, but promotes invasiveness and metastasis. GPR158, GPR110 and GPCR-X play significant roles in prostate cancer development and progression. However, GPR160 induces cell cycle arrest and apoptosis. The other major subset of orphan receptors are nuclear receptors. RORα inhibits tumor growth, but RORγ stimulates androgen receptor signaling. PXR contributes to metabolic deactivation of androgens and inhibits cell proliferation. TLX has pro-tumorigenic effects in prostate cancer, while its knockdown triggers cellular senescence and growth arrest. Estrogen-related receptor ERRγ can inhibit tumor growth but ERRα is pro-tumorigenic. Dax1 and Shp are also inhibitory in prostate cancer. Conclusion: There is a “zoo” of relatively underappreciated orphan receptors that play key roles in prostate cancer.

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Ectopic Odorant Receptor Responding to Flavor Compounds: Versatile Roles in Health and Disease

Cited by 31 publications

References 165 publications

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

OR2H2 Activation Suppresses Cellular Senescence and Aging by Activating AMPK and Inducing Senolysis in VK2/E6E7 Cells

Orphan receptors in prostate cancer

Orphan Receptors in Prostate Cancer

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