The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
A Rapid, Nongenomic, Signaling Pathway Regulates the Actin Reorganization Induced by Activation of Membrane Testosterone Receptors
Abstract
The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors, which modify the actin cytoskeleton and increase the secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid receptors are, indeed, a newly identified element of steroid action that is different from the classical intracellular sites. In the present work, using a nonpermeable analog of testosterone (testosterone-BSA), we investigated the signaling pathway that is triggered by the membrane testosterone receptors' activation and leads to actin cytoskeleton reorganization. We report that exposure of cells to testosterone-BSA resulted in phosphorylation of focal adhesion kinase (FAK), the association of FAK with the phosphatidylinositol-3 (PI-3) kinase, and the subsequent activation of the latter as well as the activation of the small guanosine triphosphatases Cdc42/Rac1. Pretreatment of cells with the specific PI-3 kinase inhibitor wortmannin abolished both the activation of the small guanosine triphosphatases and the alterations of actin cytoskeleton, whereas it did not affect the phosphorylation of FAK. These findings indicate that PI-3 kinase is activated downstream of FAK and upstream of Cdc42/Rac1, which subsequently regulate the actin organization. Moreover, wortmannin diminished the secretion of PSA, implying that the signaling events described above are responsible for the testosterone-BSA-induced PSA secretion. Our results are discussed under the prism of a possible implication of these membrane receptors in prostate cancer chemotherapy.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Androgen receptors can be modulated by specific proteins called coregulators [70–72] or mediated via the activation of membrane-bound protein receptors to initiate intracellular signalling pathways [73], which can occur even in the presence of low levels of androgens [74].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [73]
Citations
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104
Rho GTPases and the Actin Cytoskeleton
Hall, A. (1998) · Science · doi:10.1126/science.279.5350.509 · Cited by 6,138
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216
FOCAL ADHESIONS, CONTRACTILITY, AND SIGNALING
Burridge, K., & Chrzanowska‐Wodnicka, M. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.463 · Cited by 1,957
Khwaja, A., Rodriguez‐Viciana, P., Wennström, S., Warne, P. H., & Downward, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.10.2783 · Cited by 1,041
Auger, K. R., Serunian, L. A., Soltoff, S. P., Libby, P., & Cantley, L. C. (1989) · Cell · doi:10.1016/0092-8674(89)90182-7 · Cited by 910
Planat‐Benard, V., Bohl, B. P., & Bokoch, G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.19.13198 · Cited by 754
Yano, H., Nakanishi, S., Kimura, K. D., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., & Matsuda, Y. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74466-4 · Cited by 725
SPECIFIC, NONGENOMIC ACTIONS OF STEROID HORMONES
Wehling, M. (1997) · Annual Review of Physiology · doi:10.1146/annurev.physiol.59.1.365 · Cited by 663
Zhang, Z., Vuori, K., Reed, J. C., & Ruoslahti, E. I. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.13.6161 · Cited by 626
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–159 of 159
Fibroblast growth factor (Fgf) 23 gene transcription depends on actin cytoskeleton reorganization
Fajol, A., Honisch, S., Zhang, B., Schmidt, S., Alkahtani, S. H., Alarifi, S. A., Lang, F. J. W., Stournaras, C., & Föller, M. (2016) · FEBS Letters · doi:10.1002/1873-3468.12096 · Cited by 21
Self-citationPaliouras, M., & Diamandis, E. P. (2008) · Molecular Oncology · doi:10.1016/j.molonc.2008.01.001 · Cited by 21
Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor
Zhao, J., Wang, Q., Tan, A. F., Loh, C. J. L., & Toh, H. C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1416941 · Cited by 19
The histone demethylase KDM2B activates FAK and PI3K that control tumor cell motility
Zacharopoulou, N., Kallergi, G., Alkahtani, S. H., Tsapara, A., Alarifi, S. A., Schmid, E., Sukkar, B., Kampranis, S. C., Lang, F. J. W., & Stournaras, C. (2020) · Cancer Biology & Therapy · doi:10.1080/15384047.2020.1736481 · Cited by 19
Self-citationN-terminal truncations in sex steroid receptors and rapid steroid actions
Schreihofer, D. A., Duong, P., & Cunningham, R. L. (2017) · Steroids · doi:10.1016/j.steroids.2017.10.018 · Cited by 18
Zeng, N., Salker, M. S., Zhang, S., Singh, Y., Shi, B., Stournaras, C., & Lang, F. J. W. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000453197 · Cited by 18
Self-citationLiu, G., Honisch, S., Liu, G., Schmidt, S., Alkahtani, S. H., Alkahtane, A. A., Stournaras, C., & Lang, F. J. W. (2015) · BMC Cancer · doi:10.1186/s12885-015-2014-2 · Cited by 17
Self-citationIntegrins and Actions of Androgen in Breast Cancer
Tsai, C., Yang, Y. S. H., Chen, Y., Huang, L., Yang, Y., Lee, S., Wang, W., Lee, H., Whang‐Peng, J., Lin, H., et al. (2023) · Cells · doi:10.3390/cells12172126 · Cited by 16
Bungaro, M., Buttigliero, C., & Tucci, M. (2020) · Cancer Drug Resistance · doi:10.20517/cdr.2020.42 · Cited by 16
Hoque, M. T., Windus, L. C. E., Lovitt, C. J., & Avery, V. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079865 · Cited by 15
Pagliuca, S., Kulasekararaj, A. G., Eikema, D., Piepenbroek, B., Iftikhar, R., Satti, T. M., Griffin, M., Laurino, M., Küpesiz, A., Bertrand, Y., et al. (2023) · Haematologica · doi:10.3324/haematol.2023.282935 · Cited by 14
Katleba, K., Ghosh, P., & Mudryj, M. M. (2023) · Biomedicines · doi:10.3390/biomedicines11082215 · Cited by 14
Honisch, S., Alkahtani, S. H., Kounenidakis, M., Liu, G., Alarifi, S. A., Al‐Yahya, H., DIMAS, K. S., Alkahtane, A. A., Prousis, K. C., Al-Dahmash, B., et al. (2014) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520614666140618114418 · Cited by 13
Self-citationStagno, M. J., Zacharopoulou, N., Bochem, J., Tsapara, A., Pelzl, L., al‐Maghout, T., Kallergi, G., Alkahtani, S. H., Alevizopoulos, K., DIMAS, K. S., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479200 · Cited by 13
Self-citationOXER1 mediates testosterone-induced calcium responses in prostate cancer cells
Panagiotopoulos, A. A., Kalyvianaki, K., Serifoglou, B., Konstantinou, E. K., Notas, G., Castanas, E., & Kampa, M. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111487 · Cited by 12
Self-citationNeuronal differentiation of PC12 cells abolishes the expression of membrane androgen receptors
Alexaki, V. I., Dermitzaki, E., Charalampopoulos, I., Kampa, M., Nifli, A., Gravanis, A., Margioris, A. N., & Castanas, E. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.04.023 · Cited by 12
Self-citationGhatak, S., Misra, S., Moreno‐Rodriguez, R. A., Hascall, V., Leone, G. W., & Markwald, R. R. (2019) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2018.12.015 · Cited by 12
Umbayev, B. A., Saliev, T. M., Safarova, Y., Yermekova, A., Olzhayev, F., Bulanin, D. S., Tsoy, A., & Askarova, S. (2023) · Nutrients · doi:10.3390/nu15234964 · Cited by 15
Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling
Alkahtani, S. H. (2013) · Asian Journal of Andrology · doi:10.1038/aja.2013.68 · Cited by 11
Minireview: Steroid/Nuclear Receptor-Regulated Dynamics of Occluding and Anchoring Junctions
Firestone, G. L., & Kapadia, B. J. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1037 · Cited by 11
Cavalari, F. C., de Castro, A. L., Fracasso, B. D. M., & Loss, E. D. S. (2011) · Steroids · doi:10.1016/j.steroids.2011.10.014 · Cited by 10
Dias, A. B., de Oliveira, S. A., Cerri, P. S., & Sasso‐Cerri, E. (2022) · Acta Histochemica · doi:10.1016/j.acthis.2022.151873 · Cited by 9
Unzipping Androgen Action Through ZIP9: A Novel Membrane Androgen Receptor
Pascal, L. E., & Wang, Z. (2014) · Endocrinology · doi:10.1210/en.2014-1749 · Cited by 9
Gonadal hormone modulation of intracellular calcium as a mechanism of neuroprotection
Zup, S. L., & Madden, A. M. K. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.02.003 · Cited by 9
Natural extranuclear androgen receptor ligands as endocrine disruptors of cancer cell growth
Kampa, M., Notas, G., & Castanas, E. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.02.021 · Cited by 7
Self-citationDas, C., & Vijayan, M. M. (2023) · Biology · doi:10.3390/biology12020311 · Cited by 7
Flück, C. E., & Pandey, A. V. (2017) · Endocrinology · doi:10.1007/978-3-319-44441-3_10 · Cited by 7
Flück, C. E., & Pandey, A. V. (2017) · Endocrinology · doi:10.1007/978-3-319-29456-8_10-1 · Cited by 7
Dozmorov, M. G., Yang, Q., Matwalli, A., Hurst, R. E., Culkin, D. J., Kropp, B. P., & Lin, H. K. (2007) · Genomic Medicine · doi:10.1007/s11568-008-9018-9 · Cited by 5
The Functional Role of Actin Cytoskeleton Dynamics and Signaling
(2006) · Advances in molecular and cell biology · doi:10.1016/s1569-2558(06)37009-9 · Cited by 5
The Ecdysteroids' Effects in the Control of Cell Proliferation and Differentiation
Siaussat, D., Porcheron, P., & Debernard, S. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9112-4_7 · Cited by 4
Could testosterone have a therapeutic role in prostate cancer?
Stamatiou, K. N., & Pierris, N. (2013) · Urology journal./Urology jornal. · Cited by 4
Ambrosio, J. R., Arreola, M. I. P., Ríos-Valencia, D. G., Reynoso-Ducoing, O. A., Castro, K. E. N., Ostoa‐Saloma, P., & Morales‐Montor, J. (2018) · Journal of Helminthology · doi:10.1017/s0022149x18000706 · Cited by 4
Testosterone Replacement Options
McCullough, A., & Khan, M. (2022) · Urologic Clinics of North America · doi:10.1016/j.ucl.2022.07.010 · Cited by 3
Mohtadi, M. E. (2019) · e-space (Manchester Metropolitan University) · Cited by 3
Alba, E., Castaño, C., Toledano‐Díaz, A., Velázquez, R., Martínez-Madrid, B., Gómez-Crespo, A., Álvarez‐Rodríguez, M., Rodríguez‐Martínez, H., & Santiago‐Moreno, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211972 · Cited by 2
Song, J., Xue, K., She, J., Ding, F., Li, S., Shangguan, R., Dai, Y., Du, L., & Li, N. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.06.008 · Cited by 2
Androgen decreases osteoprotegerin expression in prostate cancer cells
Vandyke, K., Jackson, P., Rowe, A., Russell, P. J., & Blair, J. M. (2006) · Prostate Cancer and Prostatic Diseases · doi:10.1038/sj.pcan.4500927 · Cited by 2
McGrath, K. C. Y., Xh, L., & Williams, P. (2012) · Journal of Steroids & Hormonal Science · doi:10.4172/2157-7536.s2-005 · Cited by 2
Role of Androgens and Androgen Receptor in Prostate Cancer: Genomic and Non-Genomic Actions
Marchiani, S., Tamburrino, L., Muratori, M., Bonaccorsi, L., Forti, G., & Baldi, E. (2011) · Springer eBooks · doi:10.1007/978-1-4614-1764-4_10 · Cited by 2
Lee, M. N., Cha, S., Lim, H., & Kim, E. (2025) · Cell Biology International · doi:10.1002/cbin.70075 · Cited by 1
Flück, C. E., Yakubu, J. Y., & Pandey, A. V. (2026) · Endocrinology · doi:10.1007/978-3-319-29456-8_10-2 · Cited by 1
AKT activation participates in Fascin-1-induced EMT in hepatoma cells
Zhao, P., Ai, K., Li, Y., Cheng, W., & Ji-wu, Y. (2025) · Cytotechnology · doi:10.1007/s10616-025-00707-9 · Cited by 1
Androgen Receptor Coregulators and Their Role in Prostate Cancer
Wafa, L. A., Snoek, R., & Rennie, P. S. (2009) · Springer eBooks · doi:10.1007/978-0-387-69179-4_15 · Cited by 1
Cavalari, F. C. (2011) · Americanae (AECID Library)
MEMBRANE EFFECTS OF SEX HORMONES ON GROWTH
Chondrocytes, P. (2012)
Research Article Identification of steroid hormone signaling pathway in insect cell differentiation
Siaussat, D., Bozzolan, F., Porcheron, P., & Debernard, S. (2007)
Androgens inhibit phagocytosis by macrophages via the androgen receptor in vitro
Parry, C. (2026) · e-space (Manchester Metropolitan University) · doi:10.83056/mmu.32479596
PCP4 promotes the growth and castration-resistant development of prostate cancerPreprint
Wang, Z., Ren, J., Yin, X., Yang, P., & Liu, C. (2022) · Research Square · doi:10.21203/rs.3.rs-1522657/v1
Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer
Evans, C. P. (2008) · Defense Technical Information Center (DTIC) · doi:10.21236/ada492892
de Oliveira, E. C. (2008) · doi:10.47749/t/unicamp.2008.426173
Rho Small GTPase Family in Androgen-Regulated Prostate Cancer Progression and Metastasis
Hairston, D. W. S., Mudryj, M. M., & Ghosh, P. (2025) · Cancers · doi:10.3390/cancers17223680
Schindler, M. (2010) · theses.fr (ABES) · doi:10.70675/cee355aez4f3cz472bz8dd9z2880a141df1c
Grolez, G. P. (2018) · theses.fr (ABES) · doi:10.70675/dc6166d1z44efz4faezaf84zdeca8a743229
Sex hormones and exercise in the musculoskeletal system: from signaling to structure and function
Colicchio, C., Hernández, P., Robinson, J. L., & Connizzo, B. K. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnag018
Metadata
- Authors
- Papakonstanti, E. A., Kampa, M., Castanas, E., & Stournaras, C.
- Affiliations
- University of Crete (GR)
- Corresponding author
- Stournaras, Christos
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-05
- Volume
- 17
- Issue
- 5
- Pages
- 870-881
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2059939225
- Cited by
- 160
- References
- 74
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 11 · 2016: 4 · 2015: 2 · 2014: 10 · 2013: 7 · 2012: 6
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Olympus
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- non-genomic steroid action, actin cytoskeleton remodeling, focal adhesion kinase, phosphatidylinositol 3-kinase, Cdc42, Rac1, small GTPases, prostate-specific antigen secretion, wortmannin, prostate cancer, LNCaP cells
- MeSH terms
- Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Actins, Androstadienes, Cell Membrane, Cytoskeleton, Enzyme Inhibitors, Humans, Male, Neuropeptides, Phosphorylation, Prostatic Neoplasms, Protein-Tyrosine Kinases, Receptors, Androgen, Serum Albumin, Bovine, Dihydrotestosterone, Testosterone, Tumor Cells, Cultured, Signal Transduction, Prostate-Specific Antigen, Phosphatidylinositol 3-Kinases, rac GTP-Binding Proteins, cdc42 GTP-Binding Protein, rac1 GTP-Binding Protein, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesion Kinase 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
