Orphan receptors in prostate cancer

Sakellakis, Minas

doi:10.1002/pros.24370

Cited by 5 publications

(3 citation statements)

References 107 publications

(318 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RORA gene or also called NR1F1 (nuclear receptor subfamily 1, group F, member 1) is a transcription factor that plays a critical role in the regulation of various biological processes, including circadian rhythm, metabolism, and inflammation [ 31 ]. Recent studies have suggested that RORA may also be involved in PCa progression [ 32 ], even a RORA polymorphism rs17191414 has been associated with PCa risk, however, this data needs to be validated in other cohorts [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene

Sánchez-Martin,

Altuna-Coy,

Arreaza-Gil

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background From the first steps of prostate cancer (PCa) initiation, tumours are in contact with the most-proximal adipose tissue called periprostatic adipose tissue (PPAT). Extracellular vesicles are important carriers of non-coding RNA such as miRNAs that are crucial for cellular communication. The secretion of extracellular vesicles by PPAT may play a key role in the interactions between adipocytes and tumour. Analysing the PPAT exovesicles (EVs) derived-miRNA content can be of great relevance for understanding tumour progression and aggressiveness. Methods A total of 24 samples of human PPAT and 17 samples of perivesical adipose tissue (PVAT) were used. EVs were characterized by western blot and transmission electron microscopy (TEM), and uptake by PCa cells was verified by confocal microscopy. PPAT and PVAT explants were cultured overnight, EVs were isolated, and miRNA content expression profile was analysed. Pathway and functional enrichment analyses were performed seeking potential miRNA targets. In vitro functional studies were evaluated using PCa cells lines, miRNA inhibitors and target gene silencers. Results Western blot and TEM revealed the characteristics of EVs derived from PPAT (PPAT-EVs) samples. The EVs were up taken and found in the cytoplasm of PCa cells. Nine miRNAs were differentially expressed between PPAT and PVAT samples. The RORA gene (RAR Related Orphan Receptor A) was identified as a common target of 9 miRNA-regulated pathways. In vitro functional analysis revealed that the RORA gene was regulated by PPAT-EVs-derived miRNAs and was found to be implicated in cell proliferation and inflammation. Conclusion Tumour periprostatic adipose tissue is linked to PCa tumour aggressiveness and could be envisaged for new therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene

Sánchez-Martin,

Altuna-Coy,

Arreaza-Gil

et al. 2024

J Transl Med

View full text Add to dashboard Cite

show abstract

“…It is known that their overexpression inhibits cell proliferation and promotes cell death. Additionally, OR51E2 inhibits the growth of prostate cancer but promotes invasiveness and metastasis [ 7 , 8 ]. However, no report to date has explored the potential application of extranasal OR for diagnosis or its “druggability” in human diseases.…”

Section: Introductionmentioning

confidence: 99%

Acetate-Mediated Odorant Receptor OR51E2 Activation Results in Calcitonin Secretion in Parafollicular C-Cells: A Novel Diagnostic Target of Human Medullary Thyroid Cancer

Lee

Cho

et al. 2023

Biomedicines

View full text Add to dashboard Cite

Medullary thyroid cancer originates from parafollicular C-cells in the thyroid. Despite successful thyroidectomy, localizing remnant cancer cells in patients with elevated calcitonin and carcinoembryonic antigen levels remains a challenge. Extranasal odorant receptors are expressed in cells from non-olfactory tissues, including C-cells. This study evaluates the odorant receptor signals from parafollicular C-cells, specifically, the presence of olfactory marker protein, and further assesses the ability of the protein in localizing and treating medullary thyroid cancer. We used immunohistochemistry, immunofluorescent staining, Western blot, RNA sequencing, and real time-PCR to analyze the expression of odorant receptors in mice thyroids, thyroid cancer cell lines, and patient specimens. We used in vivo assays to analyze acetate binding, calcitonin secretion, and cAMP pathway. We also used positron emission tomography (PET) to assess C11-acetate uptake in medullary thyroid cancer patients. We investigated olfactory marker protein expression in C-cells in patients and found that it co-localizes with calcitonin in C-cells from both normal and cancer cell lines. Specifically, we found that OR51E2 and OR51E1 were expressed in thyroid cancer cell lines and human medullary thyroid cancer cells. Furthermore, we found that in the C-cells, the binding of acetate to OR51E2 activates its migration into the nucleus, subsequently resulting in calcitonin secretion via the cAMP pathway. Finally, we found that C11-acetate, a positron emission tomography radiotracer analog for acetate, binds competitively to OR51E2. We confirmed C11-acetate uptake in cancer cells and in human patients using PET. We demonstrated that acetate binds to OR51E2 in C-cells. Using C11-acetate PET, we identified recurrence sites in post-operative medullary thyroid cancer patients. Therefore, OR51E2 may be a novel diagnostic and therapeutic target for medullary thyroid cancer.

show abstract

“…Interestingly, it was noticed that the OR transcripts identified in nonolfactory tissues were not a mere representation of those present in the olfactory epithelium but a subset of the ORs encoded in the genome; even more interestingly, different subsets were identified in different tissues. Later on it was shown that the activation of OR in colorectal cells lead to inhibition of cell proliferation and apoptosis [9], and that OR play in blood pressure regulation [10] or the implication of OR 51B5 in myolenous leukemias cells [11] and more [12,13].…”

Section: Introductionmentioning

confidence: 99%

Are the Olfactory Receptors Present at the Sperm Membrane Involved in Reproduction?

Galibert

Azzouzi

2023

IJMS

View full text Add to dashboard Cite

Olfactory receptors (ORs), key components in ensuring the detection of myriad odorants, are expressed not only on the surface of olfactory neurons but also in many other tissues. In the case of ORs expressed at the sperm membrane, in vitro experiments with human and mouse spermatozoids have shown that they move toward the regions with the highest concentration of bourgeonal and lyral, respectively. However, to date, no in vivo experiment has shown any biological function of these ORs. To demonstrate a possible role in vivo of ORs in sperm chemotaxis, we overloaded the vaginal space of female mice from the prolific Swiss CD1 strain with lyral to induce competition with the supposed natural ligand and to prevent its detection. As shown, the mice that received lyral had much fewer newborns than the control mice treated with PBS, showing that lyral has a strong negative impact on procreation. This indicates that the ORs at the sperm surface are biologically active and make an important contribution to reproduction. Control experiments performed with hexanal, which does not alter sperm movement in vitro, indicate that the inhibition of reproduction observed was specific to lyral. In addition, we show that males are attracted to the smell of lyral, which acts as a pheromone, and prefer to copulate with mice marked on their back with lyral rather than with those that have not been marked. These results suggest an explanation for some cases of human infertility, which could result from an absence of recognition between the natural ligand and the ORs, either due to a mutation or a lack of expression from one of the two partners, allowing for the development of a diagnostic tests. These results might also lead to the development of a novel contraception strategy based on the use of vaginal tablets delivering an odorant or a drug that competes with the natural ligand.

show abstract

Orphan receptors in prostate cancer

Cited by 5 publications

References 107 publications

Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene

Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene

Acetate-Mediated Odorant Receptor OR51E2 Activation Results in Calcitonin Secretion in Parafollicular C-Cells: A Novel Diagnostic Target of Human Medullary Thyroid Cancer

Are the Olfactory Receptors Present at the Sperm Membrane Involved in Reproduction?

Contact Info

Product

Resources

About