The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors

Mikkel Thomsen; Morten Busk; Dalin Zhang; Chun-Lung Chiu; Hongjuan Zhao; Fernando Jose Garcia-Marques; Abel Bermudez; Sharon Pitteri; Michael Borre; James D. Brooks; Jens Randel Nyengaard

doi:10.1186/s12885-025-13928-0

The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors

Mikkel Thomsen^*, Morten Busk, Dalin Zhang, Chun-Lung Chiu, Hongjuan Zhao, Fernando Jose Garcia-Marques, Abel Bermudez, Sharon Pitteri, Michael Borre, James D. Brooks, Jens Randel Nyengaard

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Background: Despite advancements in the detection and treatment of prostate cancer, the molecular mechanisms underlying its progression remain unclear. This study aimed to investigate the role of the receptor OR51E2, which is commonly upregulated in prostate cancer, in the progression of this disease. Methods: We investigated the physiological effects of OR51E2 through CRISPR-Cas9-induced monoclonal OR51E2 knockout. We assessed in vitro and in vivo tumorigenicity and conducted transcriptomic and proteomic analyses of xenograft tumors derived from these knockout cells. Furthermore, we analyzed the effects of differences in OR51E2-expression levels in patients from a TCGA cohort. Results: OR51E2-knockout cells exhibited increased proliferation, migration, adhesion, anchorage-independent colony formation, and tumor growth rates, resulting in a more aggressive cancer phenotype. Omics analyses revealed several potential pathways associated with significant molecular changes, notably an aberration in the STAT3 pathway linked to IL-6 signaling, highlighting a connection to inflammatory pathways. TCGA cohort analysis revealed that prostate cancer patients with low tumor OR51E2 expression had a worse prognosis and a higher average Gleason grade than those with higher expression levels. Additionally, this analysis supported the putative OR51E2-related modulation of the STAT3 pathway. Conclusions: OR51E2 is regulated throughout prostate cancer progression and actively influences cancer cell physiology affecting cancer aggressiveness. Reduced OR51E2 expression may adversely affect patient outcomes, potentially through alterations in the STAT3 pathway that impact cellular responses to inflammatory signaling.

Original language	English
Article number	535
Journal	BMC Cancer
Volume	25
Issue	1
Number of pages	17
ISSN	1471-2407
DOIs	https://doi.org/10.1186/s12885-025-13928-0
Publication status	Published - Dec 2025

Keywords

Cancer physiology
Cell signaling
GPCR
Prostate cancer progression
Proteomics
Transcriptomics

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Thomsen, M., Busk, M., Zhang, D., Chiu, C.-L., Zhao, H., Garcia-Marques, F. J., Bermudez, A., Pitteri, S., Borre, M., Brooks, J. D., & Nyengaard, J. R. (2025). The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors. BMC Cancer, 25(1), Article 535. https://doi.org/10.1186/s12885-025-13928-0

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title = "The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors",

abstract = "Background: Despite advancements in the detection and treatment of prostate cancer, the molecular mechanisms underlying its progression remain unclear. This study aimed to investigate the role of the receptor OR51E2, which is commonly upregulated in prostate cancer, in the progression of this disease. Methods: We investigated the physiological effects of OR51E2 through CRISPR-Cas9-induced monoclonal OR51E2 knockout. We assessed in vitro and in vivo tumorigenicity and conducted transcriptomic and proteomic analyses of xenograft tumors derived from these knockout cells. Furthermore, we analyzed the effects of differences in OR51E2-expression levels in patients from a TCGA cohort. Results: OR51E2-knockout cells exhibited increased proliferation, migration, adhesion, anchorage-independent colony formation, and tumor growth rates, resulting in a more aggressive cancer phenotype. Omics analyses revealed several potential pathways associated with significant molecular changes, notably an aberration in the STAT3 pathway linked to IL-6 signaling, highlighting a connection to inflammatory pathways. TCGA cohort analysis revealed that prostate cancer patients with low tumor OR51E2 expression had a worse prognosis and a higher average Gleason grade than those with higher expression levels. Additionally, this analysis supported the putative OR51E2-related modulation of the STAT3 pathway. Conclusions: OR51E2 is regulated throughout prostate cancer progression and actively influences cancer cell physiology affecting cancer aggressiveness. Reduced OR51E2 expression may adversely affect patient outcomes, potentially through alterations in the STAT3 pathway that impact cellular responses to inflammatory signaling.",

keywords = "Cancer physiology, Cell signaling, GPCR, Prostate cancer progression, Proteomics, Transcriptomics",

author = "Mikkel Thomsen and Morten Busk and Dalin Zhang and Chun-Lung Chiu and Hongjuan Zhao and Garcia-Marques, {Fernando Jose} and Abel Bermudez and Sharon Pitteri and Michael Borre and Brooks, {James D.} and Nyengaard, {Jens Randel}",

year = "2025",

month = dec,

doi = "10.1186/s12885-025-13928-0",

language = "English",

volume = "25",

journal = "BMC Cancer",

issn = "1471-2407",

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The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors. / Thomsen, Mikkel ; Busk, Morten; Zhang, Dalin et al.
In: BMC Cancer, Vol. 25, No. 1, 535, 12.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors

AU - Thomsen, Mikkel

AU - Busk, Morten

AU - Zhang, Dalin

AU - Chiu, Chun-Lung

AU - Zhao, Hongjuan

AU - Garcia-Marques, Fernando Jose

AU - Bermudez, Abel

AU - Pitteri, Sharon

AU - Borre, Michael

AU - Brooks, James D.

AU - Nyengaard, Jens Randel

PY - 2025/12

Y1 - 2025/12

N2 - Background: Despite advancements in the detection and treatment of prostate cancer, the molecular mechanisms underlying its progression remain unclear. This study aimed to investigate the role of the receptor OR51E2, which is commonly upregulated in prostate cancer, in the progression of this disease. Methods: We investigated the physiological effects of OR51E2 through CRISPR-Cas9-induced monoclonal OR51E2 knockout. We assessed in vitro and in vivo tumorigenicity and conducted transcriptomic and proteomic analyses of xenograft tumors derived from these knockout cells. Furthermore, we analyzed the effects of differences in OR51E2-expression levels in patients from a TCGA cohort. Results: OR51E2-knockout cells exhibited increased proliferation, migration, adhesion, anchorage-independent colony formation, and tumor growth rates, resulting in a more aggressive cancer phenotype. Omics analyses revealed several potential pathways associated with significant molecular changes, notably an aberration in the STAT3 pathway linked to IL-6 signaling, highlighting a connection to inflammatory pathways. TCGA cohort analysis revealed that prostate cancer patients with low tumor OR51E2 expression had a worse prognosis and a higher average Gleason grade than those with higher expression levels. Additionally, this analysis supported the putative OR51E2-related modulation of the STAT3 pathway. Conclusions: OR51E2 is regulated throughout prostate cancer progression and actively influences cancer cell physiology affecting cancer aggressiveness. Reduced OR51E2 expression may adversely affect patient outcomes, potentially through alterations in the STAT3 pathway that impact cellular responses to inflammatory signaling.

AB - Background: Despite advancements in the detection and treatment of prostate cancer, the molecular mechanisms underlying its progression remain unclear. This study aimed to investigate the role of the receptor OR51E2, which is commonly upregulated in prostate cancer, in the progression of this disease. Methods: We investigated the physiological effects of OR51E2 through CRISPR-Cas9-induced monoclonal OR51E2 knockout. We assessed in vitro and in vivo tumorigenicity and conducted transcriptomic and proteomic analyses of xenograft tumors derived from these knockout cells. Furthermore, we analyzed the effects of differences in OR51E2-expression levels in patients from a TCGA cohort. Results: OR51E2-knockout cells exhibited increased proliferation, migration, adhesion, anchorage-independent colony formation, and tumor growth rates, resulting in a more aggressive cancer phenotype. Omics analyses revealed several potential pathways associated with significant molecular changes, notably an aberration in the STAT3 pathway linked to IL-6 signaling, highlighting a connection to inflammatory pathways. TCGA cohort analysis revealed that prostate cancer patients with low tumor OR51E2 expression had a worse prognosis and a higher average Gleason grade than those with higher expression levels. Additionally, this analysis supported the putative OR51E2-related modulation of the STAT3 pathway. Conclusions: OR51E2 is regulated throughout prostate cancer progression and actively influences cancer cell physiology affecting cancer aggressiveness. Reduced OR51E2 expression may adversely affect patient outcomes, potentially through alterations in the STAT3 pathway that impact cellular responses to inflammatory signaling.

KW - Cancer physiology

KW - Cell signaling

KW - GPCR

KW - Prostate cancer progression

KW - Proteomics

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=105000613067&partnerID=8YFLogxK

U2 - 10.1186/s12885-025-13928-0

DO - 10.1186/s12885-025-13928-0

M3 - Journal article

C2 - 40128715

SN - 1471-2407

VL - 25

JO - BMC Cancer

JF - BMC Cancer

IS - 1

M1 - 535

ER -

The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors

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