Androgen receptor enhances entosis, a non‐apoptotic cell death, through modulation of Rho/ROCK pathway in prostate cancer cells
Abstract
BACKGROUND: Cell‐in‐cell phenomenon has been found for more than a century. Entosis, which is a newly found homogeneous cell‐in‐cell phenomenon and a non‐apoptosis cell death progress, has unclear function in prostate cancer progression. Here, we dissected mechanism of AR signaling related to entosis incidence in PCa progression. METHODS: Two stable PCa cell lines, named LNCaP‐ARsi and C4‐2‐ARsi were established with stably transfected AR‐shRNA to knockdown AR mRNA expression in LNCaP and C4‐2 cells, respectively. PC3‐AR9 cell line was also established after stably transfecting full‐length AR‐cDNA into PC3 cells. All these cells were cultured in poly‐HEME‐coated plates to induce entosis, which is demonstrated via double staining. RESULTS: Androgen‐DHT could enhance entosis in LNCaP, C4‐2 and PC3‐AR9 PCa cells in a dose dependent manner. Knock‐down of AR in LNCaP and C4‐2 significantly suppressed entosis as compared to LNCaP‐ARsc and C4‐2‐ARsc cells at both 1 and 10 nM DHT condition (P < 0.05). And suppression of Rho/ROCK expression resulted in interruption of AR‐mediated entosis. Human PCa samples surveys demonstrated that entosis was found only in CRPC but not in BPH and ADPC where AR was less expressed as compared to CRPC. CONCLUSIONS: These results indicated that AR might play a negative role during PCa progression via influencing entosis by modulating Rho/ROCK pathway. This newly identified AR role of enhancing entosis might help us to better understand the multiple and opposite roles of AR, which could either promote or suppress PCa cell progression via different mechanisms. Prostate 73:1306–1315. © 2013 Wiley Periodicals, Inc.
Integrity signals
Registry
Cites
Statistics
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?
Entotic cell death has been documented in several human neoplasms, presumably operating as an oncosuppressor mechanism.
“Entotic cell death has been documented in several human neoplasms, presumably operating as an oncosuppressor mechanism [694, 695, 701, 709, 710].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [710]
Cites
Carver, B. S., Chapinski, C., Wongvipat, J., Hieronymus, H., Chen, Y., Chandarlapaty, S., Arora, V. K., Le, C. H., Koutcher, J. A., Scher, H. I., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.008 · Cited by 1,197 · see citing works
Transforming properties of YAP , a candidate oncogene on the chromosome 11q22 amplicon
Overholtzer, M., Zhang, J., Smolen, G. A., Muir, B., Li, W., Sgroi, D. C., Deng, C., Brugge, J. S., & Haber, D. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605579103 · Cited by 885 · see citing works
A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion
Overholtzer, M., Mailleux, A. A., Mouneimne, G., Normand, G., Schnitt, S. J., King, R. W., Cibas, E. S., & Brugge, J. S. (2007) · Cell · doi:10.1016/j.cell.2007.10.040 · Cited by 748 · see citing works
Rac and Rho GTPases in cancer cell motility control
Parri, M., & Chiarugi, P. (2010) · Cell Communication and Signaling · doi:10.1186/1478-811x-8-23 · Cited by 641 · see citing works
Rho GTPases: Signaling, Migration, and Invasion
Schmitz, A. A. P., Govek, E., Boettner, B., & Aelst, L. V. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.5049 · Cited by 578 · see citing works
Florey, O., Kim, S. E., Sandoval, C. P., Haynes, C. M., & Overholtzer, M. (2011) · Nature Cell Biology · doi:10.1038/ncb2363 · Cited by 459 · see citing works
Wildenberg, G. A., Dohn, M. R., Carnahan, R. H., Davis, M. A., Lobdell, N. A., Settleman, J. E., & Reynolds, A. B. (2006) · Cell · doi:10.1016/j.cell.2006.09.046 · Cited by 422 · see citing works
Sun, Y., Wang, B.-E., Leong, K. G., Peng, Y., Li, L., Jhunjhunwala, S., Chen, D., Seo, K., Modrusan, Z. D., Gao, W., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-3004 · Cited by 358 · see citing works
Biological Interaction Between Lymphocytes and. Other Cells
Humble, J. G., Jayne, W. H. W., & Pulvertaft, R. J. V. (1956) · British Journal of Haematology · doi:10.1111/j.1365-2141.1956.tb06700.x · Cited by 328 · see citing works
Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1
Innocenti, M., Frittoli, E., Ponzanelli, I., Falck, J. R., Brachmann, S. M., Fiore, P. P. D., & Scita, G. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200206079 · Cited by 264 · see citing works
Androgen receptor is a tumor suppressor and proliferator in prostate cancer
Niu, Y., Altuwaijri, S., Lai, K., Wu, C., Ricke, W. A., Messing, E. M., Yao, J. L., Yeh, S., & Chang, C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804700105 · Cited by 258 · see citing works
Self-citationRac signaling in breast cancer: A tale of GEFs and GAPs
Wertheimer, E. V., Gutiérrez-Uzquiza, Á., Rosemblit, C., López‐Haber, C., Sosa, M. S., & Kazanietz, M. G. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.08.011 · Cited by 204 · see citing works
A non-genetic route to aneuploidy in human cancers
Krajcovic, M., Johnson, N. B., Sun, Q., Normand, G., Hoover, N., Yao, E., Richardson, A. L., King, R. W., Cibas, E. S., Schnitt, S. J., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2174 · Cited by 188 · see citing works
Targeting the stromal androgen receptor in primary prostate tumors at earlier stages
Niu, Y., Altuwaijri, S., Yeh, S., Lai, K., Yu, S., Chuang, K., Huang, S., Lardy, H. A., & Chang, C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804701105 · Cited by 143 · see citing works
Self-citationMa, W., Hsu, C.-L., Yeh, C. C., Wu, M.-H., Huang, C.-K., Jeng, L.-B. B., Hung, Y.-C., Lin, T. Y., Yeh, S., & Chang, C. (2012) · Hepatology · doi:10.1002/hep.25644 · Cited by 138 · see citing works
Self-citationRho kinase proteins--pleiotropic modulators of cell survival and apoptosis.
Street, C. A., & Bryan, B. A. (2011) · PubMed · Cited by 114 · see citing works
Du, J., Xu, R., Hu, Z., Tian, Y., Zhu, Y., Gu, L., & Zhou, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025213 · Cited by 103 · see citing works
Bennett, H. L., Fleming, J., O’Prey, J., Ryan, K. M., & Leung, H. Y. (2010) · Cell Death and Disease · doi:10.1038/cddis.2010.50 · Cited by 78 · see citing works
Young, J. E., Garden, G. A., Martinez, R. A., Tanaka, F., Sandoval, C. M., Smith, A. C., Sopher, B. L., Lin, A., Fischbeck, K. H., Ellerby, L., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4072-08.2009 · Cited by 62 · see citing works
Mechanisms of prostate cancer cell survival after inhibition of AR expression
Cohen, M. B., & Rokhlin, O. W. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22022 · Cited by 59 · see citing works
Wan, Q., Liu, J., Zheng, Z., Zhu, H., Chu, X., Dong, Z., Huang, S., & Du, Q. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-11-0940 · Cited by 58 · see citing works
Brouwer, M., de Ley, L., Feltkamp, C. A., Elema, J. D., & Jongsma, A. (1984) · PubMed · Cited by 56 · see citing works
Emperipolesis, entosis and beyond: Dance with fate
Xia, P., Wang, S., Guo, Z. G., & Yao, X. (2008) · Cell Research · doi:10.1038/cr.2008.64 · Cited by 56 · see citing works
Entosis: It's a Cell-Eat-Cell World
White, E. (2007) · Cell · doi:10.1016/j.cell.2007.11.015 · Cited by 50 · see citing works
Progress of Research in Cell‐in‐Cell Phenomena
Yang, Y., & Li, J. (2012) · The Anatomical Record · doi:10.1002/ar.21537 · Cited by 44 · see citing works
Fleischmann, A., Rocha, C., Schobinger, S., et al. (2010) · The Prostate · doi:10.1002/pros.21259 · Cited by 38 · see citing works
Androgen deprivation and stem cell markers in prostate cancers.
Tang, Y., Hamburger, A. W., Wang, L., et al. (2009) · PubMed · Cited by 37 · see citing works
Steinhaus, J. (1891) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf01937613 · Cited by 36 · see citing works
Silencing the Metallothionein‐2A Gene Induces Entosis in Adherent MCF‐7 Breast Cancer Cells
Lai, Y., Lim, D., Tan, P., LEUNG, T. K. C., Yip, G. W. C., & Bay, B. (2010) · The Anatomical Record · doi:10.1002/ar.21215 · Cited by 25 · see citing works
Lu, S., Kim, T., Chen, C.-E., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021293 · Cited by 21 · see citing works
Differential Roles of Androgen Receptor in Prostate Development and Cancer Progression
Yeh, S., Niu, Y., Miyamoto, H., Chang, T., & Chang, C. (2009) · Springer eBooks · doi:10.1007/978-0-387-69179-4_3 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression
Buchheit, C. L., Weigel, K. J., & Schafer, Z. T. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3789 · Cited by 367 · see citing works
Entosis: Cell-in-Cell Formation that Kills Through Entotic Cell Death
Florey, O., Kim, S., & Overholtzer, M. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666151026100042 · Cited by 45 · see citing works
- Authors
- Wen, S., Shang, Z., Zhu, S., Chang, C., & Niu, Y.
- Affiliations
- Tianjin Medical University (CN)
- University of Rochester Medicine (US)
- Corresponding author
- Chang, Chawnshang
- Niu, Yuanjie
- Venue
- The Prostate
- Publisher
- Wiley
- Published
- 2013-06-15
- Volume
- 73
- Issue
- 12
- Pages
- 1306-1315
- ISSN
- 0270-4137 (ISSN-L)
- 1097-0045
- OpenAlex
- W1892659431
- Cited by
- 32
- References
- 31
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Prostate (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Basic Research Program of China (973 Program) (2012CB518304)
- International S&T Cooperation Program of China (ISTCP) (2012DFG32220)
- Important National S&T Specific Projects (2012ZX09303011-002)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Keywords
- entosis, androgen receptor, prostate cancer, Rho/ROCK signaling, non-apoptotic cell death, castration-resistant prostate cancer, prostate cancer progression, androgen receptor signaling
- MeSH terms
- Humans, Male, Prostatic Neoplasms, Receptors, Androgen, Signal Transduction, Cell Death, Cell Line, Tumor, rho-Associated Kinases, Entosis
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
