aPKCλ/ι promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6
Open accessAbstract
Understanding the mechanism by which hormone refractory prostate cancer (HRPC) develops remains a major issue. Alterations in HRPC include androgen receptor (AR) changes. In addition, the AR is activated by cytokines such as interleukin-6 (IL-6). Atypical protein kinase C (aPKClambda/iota) has been implicated in the progression of several cancers. Herein, we provide evidence that aPKClambda/iota expression correlates with prostate cancer recurrence. Experiments in vitro and in vivo revealed aPKClambda/iota to be involved in prostate cancer cell growth through secretion of IL-6. Further, aPKClambda/iota activates transcription of the IL-6 gene through NFkappaB and AP-1. We conclude that aPKClambda/iota promotes the growth of hormone independent prostate cancer cells by stimulating IL-6 production in an autocrine manner. Our findings not only explain the link between aPKClambda/iota and IL-6, implicated in the progression a variety of cancers, but also establish a molecular change involved in the development of HRPC. Further, aPKClambda/iota expression might be a biomarker for prostate cancer progression.
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IL-6 can be produced in an autocrine manner in CR prostate cells by overexpression of atypical protein kinase C (aPKC).
“Also, IL-6 can be produced in an autocrine manner in CR prostate cells by overexpression of atypical protein kinase C (aPKC/) (18).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [18]
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Cites
Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., & Thun, M. J. (2007) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.57.1.43 · Cited by 7,439 · see citing works
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F. (2003) · Biochemical Journal · doi:10.1042/bj20030407 · Cited by 3,272 · cited 1× · see citing works
“We next examined the effect of aPKC / depletion on phosphorylation of STAT3, one of the downstream mediators of the possible IL-6 involvement in prostate cancer cells (25, 29, 32, 33).”
BackgroundProtein kinase C and lipid signaling for sustained cellular responses
Nishizuka, Y. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.7.7737456 · Cited by 2,499 · see citing works
Freedland, S. J., Humphreys, E. B., Mangold, L. A., Eisenberger, M. A., Dorey, F. J., Walsh, P. C., & Partin, A. W. (2005) · JAMA · doi:10.1001/jama.294.4.433 · Cited by 1,362 · see citing works
Ohno, S. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00264-7 · Cited by 418 · see citing works
Self-citationThe interaction of p62 with RIP links the atypical PKCs to NF‐κB activation
Sanz, L., Sánchez‐Gómez, P., Lallena, M., Díaz-Meco, M. T., & Moscat, J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.11.3044 · Cited by 410 · see citing works
Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence
Taplin, M., & Balk, S. P. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10653 · Cited by 392 · see citing works
Interleukin‐6 and its receptor in cancer: Implications for Translational Therapeutics
Hong, D. S., Angelo, L. S., & Kurzrock, R. (2007) · Cancer · doi:10.1002/cncr.22999 · Cited by 370 · see citing works
Activation of IκB Kinase β by Protein Kinase C Isoforms
Lallena, M.-J., Díaz-Meco, M. T., Bren, G. D., Payá, C. V., & Moscat, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.2180 · Cited by 360 · see citing works
Serum interleukin 6 as a prognostic factor in patients with prostate cancer.
Nakashima, J., Tachibana, M., Horiguchi, Y., Oya, M., Ohigashi, T., Asakura, H., & Murai, M. (2000) · PubMed · Cited by 351 · see citing works
Freedland, S. J., Humphreys, E. B., Mangold, L. A., Eisenberger, M., Dorey, F. J., Walsh, P. C., & Partin, A. W. (2006) · The Journal of Urology · doi:10.1016/s0022-5347(05)00388-5 · Cited by 339 · see citing works
Suzuki, A., Hirata, M., Kamimura, K., Maniwa, R., Yamanaka, T., Mizuno, K., Kishikawa, M., Hirose, H., Amano, Y., Izumi, N., et al. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.021 · Cited by 319 · see citing works
Self-citationOkamoto, M., Lee, C., & Oyasu, R. (1997) · PubMed · Cited by 307 · see citing works
Androgen receptor and growth factor signaling cross-talk in prostate cancer cells.
Zhu, M.-L., & Kyprianou, N. (2008) · Endocrine Related Cancer · doi:10.1677/erc-08-0084 · Cited by 286 · see citing works
EGF or PDGF receptors activate atypical PKClambda through phosphatidylinositol 3‐kinase.
Akimoto, K., Takahashi, R., Moriya, S., Nishioka, N., Takayanagi, J., Kimura, K. D., Fukui, Y., Osada, S.-I., Mizuno, K., Hirai, S., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00414.x · Cited by 273 · see citing works
Self-citationAtypical Protein Kinase Cι Is an Oncogene in Human Non–Small Cell Lung Cancer
Regala, R. P., Weems, C. R., Jamieson, L., Khoór, A., Edell, E. S., Lohse, C. M., & Fields, A. P. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2372 · Cited by 262 · see citing works
Shariat, S. F., Andrews, B., Kattan, M. W., Kim, J., Wheeler, T. M., & Slawin, K. M. (2001) · Urology · doi:10.1016/s0090-4295(01)01405-4 · Cited by 261 · cited 1× · see citing works
“Preoperative plasma IL-6 level is related to PSA failure after radical prostatectomy (39).”
BackgroundEder, A. M., Sui, X., Rosen, D. G., Nolden, L. K., Cheng, K. W., Lahad, J. P., Kango‐Singh, M., Lu, K. H., Warneke, C. L., Atkinson, E. N., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505641102 · Cited by 238 · see citing works
Akimoto, K., Mizuno, K., Osada, S., Hirai, S.-I., Tanuma, S., Suzuki, K., & Ohno, S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99929-1 · Cited by 234 · see citing works
Self-citationA Dominant Negative Protein Kinase C ζ Subspecies Blocks NF-κ B Activation
Díaz-Meco, M. T., Berra, E., Municio, M. M., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4770-4775.1993 · Cited by 222 · see citing works
Cell Signaling and Function Organized by PB1 Domain Interactions
Moscat, J., Díaz-Meco, M. T., Albert, A., & Campuzano, S. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.002 · Cited by 195 · see citing works
STAT3 mediates IL‐6‐induced neuroendocrine differentiation in prostate cancer cells
Spiotto, M., & Chung, T. (2000) · The Prostate · doi:10.1002/(sici)1097-0045(20000215)42:3 · Cited by 191 · see citing works
Atypical Protein Kinase Cι Plays a Critical Role in Human Lung Cancer Cell Growth and Tumorigenicity
Regala, R. P., Weems, C. R., Jamieson, L., Copland, J. A., Thompson, E. A., & Fields, A. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505402200 · Cited by 181 · see citing works
Zerbini, L. F., Wang, Y., Cho, J., & Libermann, T. A. (2003) · PubMed · Cited by 171 · see citing works
Lin, D., Whitney, M. C., Yao, Z., & Keller, E. T. (2001) · PubMed · Cited by 169 · see citing works
Protein Kinase C Isoenzyme Patterns Characteristically Modulated in Early Prostate Cancer
Cornford, P. A., Evans, J., Dodson, A. R., et al. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65260-1 · Cited by 145 · see citing works
Wallner, L. P., Dai, J., Escara-Wilke, J. F., Zhang, J., Yao, Z., Lü, Y., Trikha, M., Nemeth, J. A., Zaki, M. H., & Keller, E. T. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3447 · Cited by 144 · see citing works
Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo
Murray, N. R., Jamieson, L., Yu, W., Zhang, J., Gökmen‐Polar, Y., Sier, D., Anastasiadis, P. Z., Gatalica, Z., Thompson, E. A., & Fields, A. P. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200311011 · Cited by 141 · see citing works
Tam, L., McGlynn, L. M., Traynor, P., Mukherjee, R., Bartlett, J. M. S., & Edwards, J. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603871 · Cited by 131 · see citing works
Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth
Čulig, Z., Bartsch, G. H., & Hobisch, A. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00263-0 · Cited by 131 · see citing works
Suzuki, A. (2003) · The Journal of Biochemistry · doi:10.1093/jb/mvg018 · Cited by 129 · see citing works
Zhang, L., Huang, J., Yang, N., Liang, S., Barchetti, A., Giannakakis, A., Cadungog, M. G., O’Brien-Jenkins, A., Massobrio, M., Roby, K. F., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4527 · Cited by 123 · see citing works
Smith, P. C., & Keller, E. T. (2001) · The Prostate · doi:10.1002/pros.1080 · Cited by 117 · see citing works
Royuela, M., Ricote, M., Parsons, M. S., García‐Tuñón, I., Paniagua, R., & Miguel, M. P. D. (2003) · The Journal of Pathology · doi:10.1002/path.1476 · Cited by 110 · see citing works
Genetic alterations in prostate cancer cell lines detected by comparative genomic hybridization
Nupponen, N. N., Hyytinen, E., Kallioniemi, A. H., et al. (1998) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(97)00060-5 · Cited by 101 · see citing works
Kojima, Y., Akimoto, K., Nagashima, Y., Ishiguro, H., Shirai, S., Chishima, T., Ichikawa, Y., Ishikawa, T., Sasaki, T., Kubota, Y., et al. (2008) · Human Pathology · doi:10.1016/j.humpath.2007.11.001 · Cited by 96 · see citing works
Self-citationZerbini, L. F., Wang, Y., Cho, J. Y., et al. (2004) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2003.12.016 · Cited by 86 · see citing works
Lee, S. O., Chun, J. Y., Nadiminty, N., Lou, W., & Gao, A. C. (2007) · The Prostate · doi:10.1002/pros.20553 · Cited by 85 · see citing works
Expression of protein kinase C isoenzymes in benign hyperplasia and carcinoma of prostate
Koren, R., Meir, D. B., Langzam, L., et al. (2004) · Oncology Reports · doi:10.3892/or.11.2.321 · Cited by 84 · see citing works
Current Indications for Chemotherapy in Prostate Cancer Patients
Calabrò, F., & Sternberg, C. N. (2006) · European Urology · doi:10.1016/j.eururo.2006.08.013 · Cited by 77 · see citing works
Atypical protein kinase Cλ binds and regulates p70 S6 kinase
Akimoto, K., Nakaya, M., Yamanaka, T., TANAKA, J., MATSUDA, S.-I., Qing-Ping, W. E. N. G., Avruch, J., & Ohno, S. (1998) · Biochemical Journal · doi:10.1042/bj3350417 · Cited by 74 · see citing works
Self-citationNF-κB/RelA transactivation is required for atypical protein kinase Cι-mediated cell survival
Lu, Y. C., Jamieson, L., Brasier, A. R., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204607 · Cited by 64 · see citing works
Role of Atypical Protein Kinase C in Estradiol-Triggered G1/S Progression of MCF-7 Cells
Castoria, G., Migliaccio, A., Domenico, M. D., Lombardi, M., de Falco, A., Varricchio, L., Bilancio, A., Barone, M. V., & Auricchio, F. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.17.7643-7653.2004 · Cited by 62 · see citing works
Regulation of glioblastoma cell invasion by PKCι and RhoB
Baldwin, R. M., Parolin, D. A. E., & Lorimer, I. A. J. (2008) · Oncogene · doi:10.1038/sj.onc.1211027 · Cited by 57 · see citing works
Par‐4 inducible apoptosis in prostate cancer cells
Gurumurthy, S., & Rangnekar, V. M. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20000 · Cited by 52 · see citing works
Inoue, T., Yoshida, T., Shimizu, Y., Kobayashi, T., Yamasaki, T., Toda, Y., Segawa, T., Kamoto, T., Nakamura, E., & Ogawa, O. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0033 · Cited by 50 · see citing works
Involvement of PKC‐ι in glioma proliferation
Patel, R. S., Win-Piazza, H., Desai, S., Patel, K., Matthews, J. A., & Acevedo-Duncan, M. E. (2008) · Cell Proliferation · doi:10.1111/j.1365-2184.2007.00506.x · Cited by 49 · see citing works
Bcr-Abl Regulates Protein Kinase Cι (PKCι) Transcription via an Elk1 Site in the PKCι Promoter
Gustafson, W. C., Ray, S., Jamieson, L., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312840200 · Cited by 48 · see citing works
Ghosh, P., Bedolla, R. G., Mikhailova, M., et al. (2002) · PubMed · Cited by 47 · see citing works
Corcoran, N. M., & Costello, A. J. (2003) · British Journal of Urology · doi:10.1046/j.1464-410x.2003.04025.x · Cited by 46 · see citing works
Bonizzi, G., Piette, J. G., Schoonbroodt, S., Merville, M., & Bours, V. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(98)00353-0 · Cited by 43 · see citing works
Win-Piazza, H., & Acevedo-Duncan, M. E. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.05.023 · Cited by 41 · see citing works
Li, Q., Wang, J., Liu, C., Bao-lai, X., Lu, J., & Zou, S. (2008) · PubMed · Cited by 37 · see citing works
Win, H., & Acevedo-Duncan, M. E. (2009) · Cell Proliferation · doi:10.1111/j.1365-2184.2009.00582.x · Cited by 21 · see citing works
Overexpression of p21 protein in radiation- transformed mouse 10T� cell clones
Krolewski, B., & Little, J. B. (2000) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(200002)27:2 · Cited by 6 · see citing works
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- [41]Huang C, et al. Inhibition of atypical PKC blocks ultraviolet-induced AP-1 activation by specifically inhibiting ERKs activation. Mol Carcinog. 2001;27:65–75. [PubMed] [Google Scholar]
Cited by
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Garg, R., Benedetti, L. G., Abera, M. B., Wang, H., Abba, M., & Kazanietz, M. G. (2014) · Oncogene · doi:10.1038/onc.2013.524 · Cited by 303 · see citing works
Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer
Lamont, K. R., & Tindall, D. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0469 · Cited by 150 · see citing works
PRKCI promotes immune suppression in ovarian cancer
Sarkar, S., Bristow, C. A., Dey, P., Rai, K., Perets, R., Ramirez-Cardenas, A., Malasi, S., Huang-Hobbs, E., Haemmerle, M., Wu, S. Y., et al. (2017) · Genes & Development · doi:10.1101/gad.296640.117 · Cited by 93 · see citing works
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Parker, P. J., Brown, S. J., Calleja, V., Chakravarty, P., Cobbaut, M., Linch, M., Marshall, J. J. T., Martini, S., McDonald, N. Q., Soliman, T., et al. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00310-4 · Cited by 65 · see citing works
- Authors
- Ishiguro, H., Akimoto, K., Nagashima, Y., Kojima, Y., Sasaki, T., Ishiguro-Imagawa, Y., Nakaigawa, N., Ohno, S., Kubota, Y., & Uemura, H.
- Affiliations
- Kanagawa Academy of Science and Technology (JP)
- Molecular Biology,
- Advanced Medical Research Center, Yokohama City University (JP)
- Yokohama City University (JP)
- Yokohama City University Medical Center (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09-22
- Volume
- 106
- Issue
- 38
- Pages
- 16369-16374
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2752573
- OpenAlex
- W2136199719
- Cited by
- 74
- References
- 56
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 9 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 10 · 2012: 7
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Keywords
- atypical protein kinase C, prostate cancer, castration-resistant prostate cancer, interleukin-6, autocrine signaling, androgen receptor, NF-κB, AP-1, prostate cancer recurrence, tumor cell proliferation, biomarkers
- MeSH terms
- Protein Kinase C-lambda, Aged, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Isoenzymes, Male, Neoplasm Recurrence, Local, Prostatic Neoplasms, Protein Kinase C, Blotting, Western, Transcriptional Activation, Interleukin-6, Gene Expression Regulation, Neoplastic, NF-kappa B, Disease Progression, Transcription Factor AP-1, Autocrine Communication, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Cell Line, Tumor, Cell Proliferation, Kaplan-Meier Estimate
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