Membrane androgen receptors (OXER1, GPRC6A AND ZIP9) in prostate and breast cancer: A comparative study of their expression

Kalyvianaki, Konstantina; Panagiotopoulos, Athanasios A.; Malamos, Panagiotis; Moustou, Eleni; Tzardi, Maria; Stathopoulos, Efstathios N.; Ioannidis, Georgios; Marias, Kostas; Notas, George; Theodoropoulos, Panayiotis A.; Castanas, Elias; Kampa, Marilena

doi:10.1016/j.steroids.2019.01.006

Cited by 34 publications

(42 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results were observed in SLC39A9. SLC39A9 also portrayed as mAR that related to the extranuclear action of androgens in BC cells [41]. Chen et al found that androgen and dihydrotestosterone (DHT) increased migration and invasion of nuclear androgen receptor (nAR)-negative bladder cancer cells via a newly identified membrane AR-SLC39A9-mediated intracellular signaling [42].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer

2020

View full text Add to dashboard Cite

Background: Breast cancer (BC) is the most common malignancy in females and remains a main cause of cancer-associated death worldwide. The solute carrier (SLC) groups of membrane transport proteins, which control the inﬂux of zinc, participate in ranging of physiological processes and may provide novel therapeutic targets of cancers. However, the prognostic values of individual SLC family 39 (SLC39A) genes in patients with BC are not clarified. Materials and Methods: The mRNA expression of SLC family 39 genes in BC was evaluated by using the UALCAN database. The prognostic values of overall survival (OS) of SLC family 39 genes in patients with BC were investigated by Kaplan-Meier plotter. The survival analysis of cells was determined by Project Achilles. Results: The analytic results suggested that SLC39A1, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A9, SLC39A10, SLC39A11 and SLC39A13 were significantly upregulated in BC tissues compared with normal breast tissues. However, SLC39A8 and SLC39A14 were expressed higher in normal tissues than in BC tissues. High expression of SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A7, SLC39A12 and SLC39A13 was significantly associated with worse OS in patients with BC. In contrast, high mRNA levels of SLC39A6 and SLC39A14 indicated favorable OS. Through subgroup analysis, all abnormal expressed SLC family members were correlated with prognoses of patients with specific BC. Moreover, SLC39A7 was associated with proliferation and cloning of BC. Conclusions: Our results suggested that SLC family 39 members were promising prognostic biomarkers of BC. The SLC39A7 played a key role in growth and survival of BC cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer

2020

View full text Add to dashboard Cite

show abstract

“…Multiple groups have also studied the role of cytoplasmic AR phosphorylation 49,50 ; however, additional work is required to understand how AR modifications influence cellular function and localization. At the membrane, many receptors mediate rapid responses to androgen signaling, representing novel membrane-ARs 51,52 . These signals, however, are complex as agonistic verses antagonistic effects are dependent on receptor stoichiometry 52 .…”

Section: Ar and Ptenmentioning

confidence: 99%

“…At the membrane, many receptors mediate rapid responses to androgen signaling, representing novel membrane-ARs 51,52 . These signals, however, are complex as agonistic verses antagonistic effects are dependent on receptor stoichiometry 52 . Furthermore, AR is expressed in fibrosarcoma cells; however, a significant portion of AR is transcriptionally incompetent and does not bind to AREs upon activation.…”

Section: Ar and Ptenmentioning

confidence: 99%

ARe we there yet? Understanding androgen receptor signaling in breast cancer

et al. 2020

View full text Add to dashboard Cite

The role of androgen receptor (AR) activation and expression is well understood in prostate cancer. In breast cancer, expression and activation of AR is increasingly recognized for its role in cancer development and its importance in promoting cell growth in the presence or absence of estrogen. As both prostate and breast cancers often share a reliance on nuclear hormone signaling, there is increasing appreciation of the overlap between activated cellular pathways in these cancers in response to androgen signaling. Targeting of the androgen receptor as a monotherapy or in combination with other conventional therapies has proven to be an effective clinical strategy for the treatment of patients with prostate cancer, and these therapeutic strategies are increasingly being investigated in breast cancer. This overlap suggests that targeting androgens and AR signaling in other cancer types may also be effective. This manuscript will review the role of AR in various cellular processes that promote tumorigenesis and metastasis, first in prostate cancer and then in breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of cancer, especially breast cancer.

show abstract

“…A number of rapid, plasma membrane located androgen signalling pathways independent of the AR have been identified over the last decade 38 . One such pathway is the direct inhibitory action of androgens on L-type calcium channels (LTCC) [39][40][41][42][43] .…”

Section: Development Of a Strategy For Chemical Library Screening In mentioning

confidence: 99%

A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2−/− phenotype

Metzner

Griffiths

Streets

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of end-stage renal failure in humans and results from germline mutations in PKD1 or PKD2. Despite the recent approval of tolvaptan, safer and more effective alternative drugs are clearly needed to slow disease progression. As a first step in drug discovery, we conducted an unbiased chemical screen on zebrafish pkd2 mutant embryos using two publicly available compound libraries (Spectrum, PKIS) totalling 2,367 compounds to identify novel treatments for ADPKD. Using dorsal tail curvature as the assay readout, three major chemical classes (steroids, coumarins, flavonoids) were identified from the Spectrum library as the most promising candidates to be tested on human PKD1 cystic cells. Amongst these were an androgen, 5α−androstane 3,17-dione, detected as the strongest enhancer of the pkd2 phenotype but whose effect was found to be independent of the canonical androgen receptor pathway. From the PKIS library, we identified several ALK5 kinase inhibitors as strong suppressors of the pkd2 tail phenotype and in vitro cyst expansion. In summary, our results identify ALK5 and non-canonical androgen receptors as potential therapeutic targets for further evaluation in drug development for ADPKD.

show abstract

Membrane androgen receptors (OXER1, GPRC6A AND ZIP9) in prostate and breast cancer: A comparative study of their expression

Cited by 34 publications

References 44 publications

Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer

Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer

ARe we there yet? Understanding androgen receptor signaling in breast cancer

A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2−/− phenotype

Contact Info

Product

Resources

About