The NF-κB subunit RelB regulates the migration and invasion abilities and the radio-sensitivity of prostate cancer cells
Abstract
NF-κB subunits play important roles in carcinogenesis of a variety of human malignancies and response to cancer therapy; however, the contribution of an individual subunit has not been thoroughly defined. Constitutive activation of the canonical NF-κB subunit is a critical event in prostate carcinogenesis. Recent findings point out that RelB, which contributes to the non-canonical NF-κB activity, functions importantly in the prostate cancer progression. Here, we investigated systemically the functional roles of RelB in prostate cancer and examine its significance as a therapeutic target. Targeting RelB using short hairpin RNA approach in androgen-independent DU145 prostate cancer cells interfered with various biological behaviors of cells. We observed that RelB knockdown inhibited prostate cancer cell growth, migration, and invasion, and enhanced proteasome inhibitor sensitivity. The altered expression of anti-apoptotic gene Bcl-2 played critical roles in regulating both spontaneous and radiation-induced apoptosis in the presence of RelB knockdown. For the first time, we showed that RelB knockdown significantly attenuated the migration and invasion of DU145 prostate cancer cells, due to the reduction of integrin β-1. Collectively, we provided evidence that RelB functioned as an oncogene in prostate cancer. Developing a RelB-targeted therapeutic intervention, is valuable in treating advanced, metastatic prostate cancer.
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These findings are in line with reported roles for the noncanonical NF-κB pathway in EMT, cellular invasion, and metastasis.
“These findings are in line with reported roles for the noncanonical NF-κB pathway in EMT, cellular invasion, and metastasis33–35.”
From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [34]
The Discussion (p. 10) reports a role for RelB, a noncanonical NF-κB subunit, in EMT in breast cancer cells and shows that RelB knockdown reduced invasion in prostate cancer cells. It discusses links to metastasis, but does not establish that RelB itself promotes metastasis; the authors say in vivo studies remain for future work (Discussion, p. 11). (LLM, conf=0.86)
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1 retracted
Wang, X., Li, J., Yan, M., Liu, L., Jia, D., Qin, G., Lin, H., He, X., Li, J., & Yao, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055714 · Cited by 98 · see citing works
RetractedNuclear factor-κB in cancer development and progression
Karin, M. (2006) · Nature · doi:10.1038/nature04870 · Cited by 3,519 · see citing works
Molecular Basis of NF-κB Signaling
Napetschnig, J., & Wu, H. (2013) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-083012-130338 · Cited by 940 · see citing works
The diverse and complex roles of NF-κB subunits in cancer
Perkins, N. D. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3204 · Cited by 845 · see citing works
Cancer statistics for Hispanics/Latinos, 2015
Siegel, R. L., Fedewa, S. A., Miller, K. D., Sauer, A. G., Pinheiro, P. S., Martinez‐Tyson, D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21314 · Cited by 467 · see citing works
Nuclear cytokine-activated IKKα controls prostate cancer metastasis by repressing Maspin
Luo, J., Tan, W., Ricono, J. M., Korchynskyi, O., Zhang, M., Gonias, S. L., Cheresh, D. A., & Karin, M. (2007) · Nature · doi:10.1038/nature05656 · Cited by 436 · see citing works
NF‐κB activation in human prostate cancer: Important mediator or epiphenomenon?
Suh, J., & Rabson, A. B. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10729 · Cited by 224 · see citing works
Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2
Wang, X., Belguise, K., Kersual, N., Kirsch, K. H., Mineva, N. D., Galtier, F., Chalbos, D., & Sonenshein, G. E. (2007) · Nature Cell Biology · doi:10.1038/ncb1559 · Cited by 209 · see citing works
Weih, F., & Caamaño, J. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00064.x · Cited by 201 · see citing works
Lessard, L., Bégin, L. R., Gleave, M. E., Mes‐Masson, A., & Fred Saad, C. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602796 · Cited by 140 · see citing works
Apigenin blocks IKKα activation and suppresses prostate cancer progression
Shukla, S., Kanwal, R., Shankar, E., Datt, M., Chance, M. R., Fu, P., MacLennan, G. T., & Gupta, S. (2015) · Oncotarget · doi:10.18632/oncotarget.5157 · Cited by 107 · see citing works
Targeting Constitutively Activated β1 Integrins Inhibits Prostate Cancer Metastasis
Lee, Y.-C., Jin, J.-K., Cheng, C.-J., Huang, C., Song, J. H., Huang, M. L., Brown, W. S., Zhang, S., Yu‐Lee, L., Yeh, E. T. H., et al. (2013) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0551 · Cited by 90 · see citing works
Bax and Bcl-2 expressions predict response to radiotherapy in human cervical cancer
Harima, Y., Harima, K., Shikata, N., Oka, A., Ohnishi, T., & Tanaka, Y. (1998) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s004320050206 · Cited by 86 · see citing works
Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for survival
Ranuncolo, S. M., Pittaluga, S., Evbuomwan, M. O., Jaffe, E. S., & Lewis, B. A. (2012) · Blood · doi:10.1182/blood-2012-01-405951 · Cited by 76 · see citing works
Xu, Y., Josson, S., Fang, F., Oberley, T. D., Clair, D. K. S., Wan, X. S., Sun, Y., Bakthavatchalu, V., Muthuswamy, A., & Clair, W. H. S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4635 · Cited by 74 · see citing works
RelB NF-κB Represses Estrogen Receptor α Expression via Induction of the Zinc Finger Protein Blimp1
Wang, X., Belguise, K., O’Neill, C. F., Sánchez-Morgan, N., Romagnoli, M., Eddy, S. F., Mineva, N. D., Yu, Z., Min, C., Trinkaus‐Randall, V., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00032-09 · Cited by 72 · see citing works
Peeters, M. C., Fokkelman, M., Boogaard, B., Egerod, K. L., van de Water, B., IJzerman, A. P., & Schwartz, T. W. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.08.015 · Cited by 67 · see citing works
Singha, B., Gatla, H. R., Manna, S., Chang, T., Sanacora, S., Poltoratsky, V. P., Vančura, A., & Vancurova, I. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.502641 · Cited by 66 · see citing works
Xu, Y., Fang, F., Clair, D. K. S., Josson, S., Sompol, P. M., Spasojević, I., & Clair, W. H. S. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0700 · Cited by 62 · see citing works
Xu, Y., Fang, F., Clair, D. K. S., Sompol, P. M., Josson, S., & Clair, W. H. S. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0238 · Cited by 59 · see citing works
Holley, A. K., Xu, Y., Clair, D. K. S., & Clair, W. H. S. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05613.x · Cited by 57 · see citing works
Guo, F., Sun, A., Wang, W., He, J., Hou, J., Zhou, P., & Chen, Z. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.05.178 · Cited by 56 · see citing works
Self-citationG-helix of Maspin Mediates Effects on Cell Migration and Adhesion
Ravenhill, L., Wagstaff, L., Edwards, D. R., Ellis, V., & Bass, R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.177253 · Cited by 45 · see citing works
Mineva, N. D., Wang, X., Yang, S., Ying, H., Xiao, Z. J., Holick, M. F., & Sonenshein, G. E. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21765 · Cited by 41 · see citing works
Frequent Engagement of RelB Activation Is Critical for Cell Survival in Multiple Myeloma
Cormier, F., Monjanel, H., Fabre, C., Billot, K., Sapharikas, E., Chéreau, F., Bordereaux, D., Molina, T. J., Avet‐Loiseau, H., & Baud, V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059127 · Cited by 38 · see citing works
Manna, S., Singha, B., Phyo, S. A., Gatla, H. R., Chang, T., Sanacora, S., Ramaswami, S., & Vancurova, I. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300895 · Cited by 32 · see citing works
Xu, J., Zhou, P., Wang, W., Sun, A., & Guo, F. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1081-6 · Cited by 32 · see citing works
Self-citationYu, Z., Sato, S., Trackman, P. C., Kirsch, K. H., & Sonenshein, G. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033287 · Cited by 30 · see citing works
Authier, H., Billot, K., Derudder, E., Bordereaux, D., Rivière, P., Rodrigues, S., Nahmias, C., & Baud, V. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410124111 · Cited by 28 · see citing works
Lessard, L., Fred Saad, C., Page, C. L., Diallo, J., Péant, B., Delvoye, N., & Mes‐Masson, A. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2006.12.012 · Cited by 28 · see citing works
RelB-Dependent Differential Radiosensitization Effect of STI571 on Prostate Cancer Cells
Xu, Y., Fang, F., Sun, Y., Clair, D. K. S., & Clair, W. H. S. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-1001 · Cited by 24 · see citing works
Zhu, L., Zhu, B., Yang, L., Zhao, X., JIANG, H., & Ma, F. (2014) · Biomedical Reports · doi:10.3892/br.2014.250 · Cited by 21 · see citing works
Xie, B.-X., Zhang, H., Lan, Y., Wang, J., Pang, B., Wu, R.-Q., Qian, X. L., Li, S.-H., Shi, Q., Wang, L.-L., et al. (2010) · Asian Journal of Andrology · doi:10.1038/aja.2009.91 · Cited by 20 · see citing works
Self-citationXu, Y., Fang, F., Clair, D. K. S., & Clair, W. H. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032905 · Cited by 12 · see citing works
p52-independent nuclear translocation of RelB promotes LPS-induced attachment
Saito, T., Sasaki, C. Y., Rezanka, L. J., Ghosh, P., & Longo, D. L. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.11.039 · Cited by 11 · see citing works
Guo, F., Kang, S., Zhou, P., Guo, L., Ma, L., & Hou, J. (2011) · Molecular Immunology · doi:10.1016/j.molimm.2011.07.013 · Cited by 11 · see citing works
Self-citationDifferent maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines
Zhou, J., Qin, H., Zhou, P., & Guo, F. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2336 · Cited by 6 · see citing works
Self-citationGene Mutation Revelation Points to New Target for Myeloma Treatment, Studies Say
Garber, K. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm164 · Cited by 2 · see citing works
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Bakhoum, S. F., Ngo, B., Laughney, A. M., Cavallo, J.-A., Murphy, C. J., Ly, P., Shah, P., Sriram, R. K., Watkins, T. B. K., Taunk, N. K., et al. (2018) · Nature · doi:10.1038/nature25432 · Cited by 1,638 · see citing works
Inflammation and NF-κB Signaling in Prostate Cancer: Mechanisms and Clinical Implications
Staal, J., & Beyaert, R. (2018) · Cells · doi:10.3390/cells7090122 · Cited by 103 · see citing works
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Thomas-Jardin, S. E., Dahl, H., Nawas, A. F., Bautista, M., & Delk, N. A. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107538 · Cited by 99 · see citing works
Oseni, S. O., Naar, C., Pavlović, M. D., Asghar, W., Hartmann, J. X., Fields, G. B., Esiobu, N., & Kumi-Diaka, J. K. (2023) · Cancers · doi:10.3390/cancers15123110 · Cited by 94 · see citing works
cGAS–STING signalling in cancer: striking a balance with chromosomal instability
Beernaert, B., & Parkes, E. E. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220838 · Cited by 59 · see citing works
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Hong, C., Tijhuis, A. E., & Foijer, F. (2019) · Cells · doi:10.3390/cells8101228 · Cited by 55 · see citing works
Baci, D., Gallazzi, M., Cascini, C., Tramacere, M., Stefano, D. D., Bruno, A., Noonan, D. M., & Albini, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020307 · Cited by 49 · see citing works
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Talens, F., & van Vugt, M. A. T. M. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1638192 · Cited by 42 · see citing works
Domińska, K., Kowalska, K., MATYSIAK-BURZYŃSKA, Z. E., Płuciennik, E., Ochędalski, T., & Piastowska‐Ciesielska, A. W. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6514 · Cited by 23 · see citing works
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Wanjari, U. R., Mukherjee, A. G., Gopalakrishnan, A. V., Murali, R., Dey, A., Vellingiri, B., & Ganesan, R. (2023) · Metabolites · doi:10.3390/metabo13020183 · Cited by 22 · see citing works
RelB plays an oncogenic role and conveys chemo-resistance to DLD-1 colon cancer cells
Zhou, X., Shan, Z., Yang, H., Xu, J., Li, W., & Guo, F. (2018) · Cancer Cell International · doi:10.1186/s12935-018-0677-x · Cited by 20 · see citing works
Self-citationDimitrakopoulos, F., Antonacopoulou, A., Kottorou, A., Panagopoulos, N., Kalofonou, F., Sampsonas, F., Scopa, C., Kalofonou, M., Koutras, A., Makatsoris, T., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50528-y · Cited by 22 · see citing works
Wang, D., Yan, K. H., Yu, H., Li, H., Zhou, W., Hong, Y., Guo, S., Wang, Y., Xu, C., Pan, C., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0394 · Cited by 18 · see citing works
The Role of the Toll-like Receptor 2 and the cGAS-STING Pathways in Breast Cancer: Friends or Foes?
Cossu, C., Lorenzo, A. D., Fiorilla, I., Todesco, A. M., Audrito, V., & Conti, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010456 · Cited by 19 · see citing works
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Li, W., Xu, J., Cheng, L., Zhao, C., Zhang, L., Shao, Q., & Guo, F. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110221 · Cited by 16 · see citing works
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Radwan, E., Ali, M., Faied, S. M. A., Omar, H. E.-D. M., Mohamed, W. S., Abd‐Elghaffar, S. K., & Sayed, A. A.-R. (2020) · IUBMB Life · doi:10.1002/iub.2432 · Cited by 14 · see citing works
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Harper, E., Rochfort, K. D., Forde, H. E., Davenport, C., Smith, D., & Cummins, P. M. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.04.004 · Cited by 10 · see citing works
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- Authors
- WANG, J., YI, S., ZHOU, J., ZHANG, Y., & GUO, F.
- Affiliations
- First Affiliated Hospital of Soochow University (CN)
- Yancheng First People's Hospital (CN)
- Venue
- International Journal of Oncology
- Publisher
- Spandidos Publications
- Published
- 2016-04-25
- Volume
- 49
- Issue
- 1
- Pages
- 381-392
- ISSN
- 1019-6439 (ISSN-L)
- 1791-2423
- OpenAlex
- W2342747098
- Cited by
- 25
- References
- 38
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 7 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- RelB, NF-κB subunits, prostate cancer, cell migration, cell invasion, radiosensitivity, Bcl-2, apoptosis, beta1 integrin, oncogenes, non-canonical NF-κB, therapeutic target
- MeSH terms
- Cell Movement, Humans, Male, Neoplasm Invasiveness, Neoplasm Metastasis, Prostatic Neoplasms, Radiation Tolerance, Signal Transduction, Gene Expression Regulation, Neoplastic, Apoptosis, Integrin beta1, Proto-Oncogene Proteins c-bcl-2, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation, Transcription Factor RelB, Proteasome Inhibitors
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