Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer.
Animals
Antineoplastic Agents
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ genetics
Disease Models, Animal
Drug Resistance, Neoplasm
/ genetics
Gene Expression Regulation
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
HEK293 Cells
Hepatocyte Nuclear Factor 3-alpha
/ metabolism
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Nuclear Respiratory Factor 1
/ metabolism
Octamer Transcription Factor-3
/ genetics
Prostatic Neoplasms, Castration-Resistant
/ genetics
Receptors, Androgen
/ metabolism
Ribavirin
/ pharmacology
Signal Transduction
Transcriptome
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 06 2021
18 06 2021
Historique:
received:
30
07
2020
accepted:
19
05
2021
entrez:
19
6
2021
pubmed:
20
6
2021
medline:
7
7
2021
Statut:
epublish
Résumé
Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.
Identifiants
pubmed: 34145268
doi: 10.1038/s41467-021-23974-4
pii: 10.1038/s41467-021-23974-4
pmc: PMC8213733
doi:
Substances chimiques
Antineoplastic Agents
0
Foxa1 protein, mouse
0
Hepatocyte Nuclear Factor 3-alpha
0
Nrf1 protein, mouse
0
Nuclear Respiratory Factor 1
0
Octamer Transcription Factor-3
0
Pou5f1 protein, mouse
0
Receptors, Androgen
0
Ribavirin
49717AWG6K
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3766Commentaires et corrections
Type : CommentIn
Références
Viswanathan, S. R. et al. Structural alterations driving castration-resistant prostate cancer revealed by linked-read genome sequencing. Cell 174, 433–447 (2018).
pmcid: 6046279
doi: 10.1016/j.cell.2018.05.036
pubmed: 29909985
Grasso, C. S. et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 487, 239–243 (2012).
pmcid: 3396711
doi: 10.1038/nature11125
pubmed: 22722839
Chen, C. D. et al. Molecular determinants of resistance to antiandrogen therapy. Nat. Med. 10, 33–39 (2004).
doi: 10.1038/nm972
pubmed: 14702632
Davies, A. H., Beltran, H. & Zoubeidi, A. Cellular plasticity and the neuroendocrine phenotype in prostate cancer. Nat. Rev. Urol. 15, 271–286 (2018).
doi: 10.1038/nrurol.2018.22
pubmed: 29460922
Takayama, K. et al. Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF. Proc. Natl Acad. Sci. USA 114, 10461–10466 (2017).
doi: 10.1073/pnas.1706076114
pubmed: 28893982
pmcid: 5625911
Lupien, M. et al. FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132, 958–970 (2008).
pmcid: 2323438
doi: 10.1016/j.cell.2008.01.018
pubmed: 18358809
Sharma, N. L. et al. The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man. Cancer Cell 23, 35–47 (2013).
doi: 10.1016/j.ccr.2012.11.010
pubmed: 23260764
Vidal, S. J. et al. A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer. Cancer Cell 27, 223–239 (2015).
pmcid: 4356948
doi: 10.1016/j.ccell.2014.11.013
pubmed: 25670080
Wang, Q. et al. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell 138, 245–256 (2009).
pmcid: 2726827
doi: 10.1016/j.cell.2009.04.056
pubmed: 19632176
Chen, X. et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106–1117 (2008).
doi: 10.1016/j.cell.2008.04.043
pubmed: 18555785
Wang, Q. et al. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol. Cell 27, 380–392 (2007).
pmcid: 3947890
doi: 10.1016/j.molcel.2007.05.041
pubmed: 17679089
Jin, H. J., Zhao, J. C., Wu, L., Kim, J. & Yu, J. Cooperativity and equilibrium with FOXA1 define the androgen receptor transcriptional program. Nat. Commun. 5, 3972 (2014).
doi: 10.1038/ncomms4972
pubmed: 24875621
Dardenne, E. et al. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell 30, 563–577 (2016).
pmcid: 5540451
doi: 10.1016/j.ccell.2016.09.005
pubmed: 27728805
Mu, P. et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 355, 84–88 (2017).
pmcid: 5247742
doi: 10.1126/science.aah4307
pubmed: 28059768
Rotinen, M. et al. ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis. Nat. Med. 24, 1887–1898 (2018).
pmcid: 6614557
doi: 10.1038/s41591-018-0241-1
pubmed: 30478421
Guo, H. et al. ONECUT2 is a driver of neuroendocrine prostate cancer. Nat. Commun. 10, 278 (2019).
pmcid: 6336817
doi: 10.1038/s41467-018-08133-6
pubmed: 30655535
Alberti, S. Phase separation in biology. Curr. Biol. 27, R1097–R1102 (2017).
doi: 10.1016/j.cub.2017.08.069
pubmed: 29065286
Boija, A. et al. Factors activate genes through the phase separation capacity of their activation domains. Cell 175, 1842–1855 (2018). e16.
doi: 10.1016/j.cell.2018.10.042
pubmed: 30449618
Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).
pmcid: 7434221
doi: 10.1038/nrm.2017.7
pubmed: 28225081
Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017).
doi: 10.1126/science.aaf4382
pubmed: 28935776
Wright, P. E. & Dyson, H. J. Intrinsically disordered proteins in cellular signalling and regulation. Nat. Rev. Mol. Cell Biol. 16, 18–29 (2015).
pmcid: 4405151
doi: 10.1038/nrm3920
pubmed: 25531225
Nott, T. J. et al. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol. Cell 57, 936–947 (2015).
pmcid: 4352761
doi: 10.1016/j.molcel.2015.01.013
pubmed: 25747659
Nair, S. J. et al. Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nat. Struct. Mol. Biol. 26, 193–203 (2019).
pmcid: 6709854
doi: 10.1038/s41594-019-0190-5
pubmed: 30833784
Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K. & Sharp, P. A. A phase separation model for transcriptional control. Cell 169, 13–23 (2017).
pmcid: 5432200
doi: 10.1016/j.cell.2017.02.007
pubmed: 28340338
Guo, Y. E. et al. Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Nature 572, 543–548 (2019).
pmcid: 6706314
doi: 10.1038/s41586-019-1464-0
pubmed: 31391587
Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
doi: 10.1016/j.cell.2007.11.019
pubmed: 18035408
Brehm, A. et al. Synergism with germ line transcription factor Oct-4: viral oncoproteins share the ability to mimic a stem cell-specific activity. Mol. Cell Biol. 19, 2635–2643 (1999).
pmcid: 84056
doi: 10.1128/MCB.19.4.2635
pubmed: 10082529
Takayama, K., Fujimura, T., Suzuki, Y. & Inoue, S. Identification of long non-coding RNAs in advanced prostate cancer associated with androgen receptor splicing factors. Commun. Biol. 3, 393 (2020).
pmcid: 7378231
doi: 10.1038/s42003-020-01120-y
pubmed: 32704143
Aytes, A. et al. Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell 25, 638–651 (2014).
pmcid: 4051317
doi: 10.1016/j.ccr.2014.03.017
pubmed: 24823640
Kosaka, T. et al. Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming. Cancer Sci. 104, 1017–1026 (2013).
pmcid: 7657195
doi: 10.1111/cas.12183
pubmed: 23600803
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2011).
doi: 10.1016/j.molcel.2010.05.004
Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934–947 (2013).
doi: 10.1016/j.cell.2013.09.053
pubmed: 24119843
Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307–319 (2013).
pmcid: 3653129
doi: 10.1016/j.cell.2013.03.035
pubmed: 23582322
Triezenberg, S. J. Structure and function of transcriptional activation domains. Curr. Opin. Genet Dev. 5, 190–196 (1995).
doi: 10.1016/0959-437X(95)80007-7
pubmed: 7613088
Kato, M. et al. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149, 753–767 (2012).
pmcid: 6347373
doi: 10.1016/j.cell.2012.04.017
pubmed: 22579281
Sabari, B. R. et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science 361, eaar3958 (2018).
pmcid: 6092193
doi: 10.1126/science.aar3958
pubmed: 29930091
Kroschwald, S. et al. Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules. Elife 4, e06807 (2015).
pmcid: 4522596
doi: 10.7554/eLife.06807
pubmed: 26238190
Feld, J. J. & Hoofnagle, J. H. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature 436, 967–972 (2005).
doi: 10.1038/nature04082
pubmed: 16107837
Fried, M. W. et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N. Engl. J. Med. 347, 975–982 (2002).
doi: 10.1056/NEJMoa020047
pubmed: 12324553
Lui, M. S. et al. Modulation of IMP dehydrogenase activity and guanylate metabolism by tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide). J. Biol. Chem. 259, 5078–5082 (1984).
doi: 10.1016/S0021-9258(17)42958-9
pubmed: 6143752
Kentsis, A., Topisirovic, I., Culjkovic, B., Shao, L. & Borden, K. L. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc. Natl Acad. Sci. USA 101, 18105–18110 (2004).
doi: 10.1073/pnas.0406927102
pubmed: 15601771
pmcid: 539790
Franchetti, P. & Grifantini, M. Nucleoside and non-nucleoside IMP dehydrogenase inhibitors as antitumor and antiviral agents. Curr. Med. Chem. 6, 599–614 (1999).
pubmed: 10390603
doi: 10.2174/092986730607220401123801
Wu, Z. et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115–124 (1999).
doi: 10.1016/S0092-8674(00)80611-X
pubmed: 10412986
Duteil, D. et al. LSD1 promotes oxidative metabolism of white adipose tissue. Nat. Commun. 5, 4093 (2014).
doi: 10.1038/ncomms5093
pubmed: 24912735
Zhang, J. et al. EglN2 associates with the NRF1-PGC1α complex and controls mitochondrial function in breast cancer. EMBO J. 34, 2953–2970 (2015).
pmcid: 4687683
doi: 10.15252/embj.201591437
pubmed: 26492917
Rojo de la Vega, M., Chapman, E. & Zhang, D. D. NRF2 and the hallmarks of cancer. Cancer Cell 34, 21–43 (2018).
doi: 10.1016/j.ccell.2018.03.022
pubmed: 29731393
Pritchard, C. C. et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N. Engl. J. Med. 375, 443–453 (2016).
pmcid: 4986616
doi: 10.1056/NEJMoa1603144
pubmed: 27433846
Li, L. et al. Androgen receptor inhibitor-induced “BRCAness” and PARP inhibition are synthetically lethal for castration-resistant prostate cancer. Sci. Signal 10, eaam7479 (2017).
pmcid: 5855082
doi: 10.1126/scisignal.aam7479
pubmed: 28536297
Richards, L. Prostate cancer: cabazitaxel boosts post-docetaxel survival. Nat. Rev. Urol. 7, 645 (2010).
doi: 10.1038/nrurol.2010.200
pubmed: 21188774
Hongo, H., Kosaka, T. & Oya, M. Analysis of cabazitaxel-resistant mechanism in human castration-resistant prostate cancer. Cancer Sci. 109, 2937–2945 (2018).
pmcid: 6125448
doi: 10.1111/cas.13729
pubmed: 29989268
Kosaka, T. et al. The prognostic significance of OCT4 expression in patients with prostate cancer. Hum. Pathol. 51, 1–8 (2016).
doi: 10.1016/j.humpath.2015.12.008
pubmed: 27067776
Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat. Med. 22, 298–305 (2016).
pmcid: 4777652
doi: 10.1038/nm.4045
pubmed: 26855148
Robinson, D. et al. Integrative clinical genomics of advanced prostate cancer. Cell 161, 1215–1228 (2015).
pmcid: 4484602
doi: 10.1016/j.cell.2015.05.001
pubmed: 26000489
Abida, W. et al. Genomic correlates of clinical outcome in advanced prostate cancer. Proc. Natl Acad. Sci. USA 116, 11428–11436 (2019).
doi: 10.1073/pnas.1902651116
pubmed: 31061129
pmcid: 6561293
Wang, S., Gao, D. & Chen, Y. The potential of organoids in urological cancer research. Nat. Rev. Urol. 14, 401–414 (2017).
pmcid: 5558053
doi: 10.1038/nrurol.2017.65
pubmed: 28534535
Shiba, S. et al. Hormonal regulation of patient-derived endometrial cancer stem-like cells generated by three-dimensional culture. Endocrinology 160, 1895–1906 (2019).
doi: 10.1210/en.2019-00362
pubmed: 31265065
Lovén, J. et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153, 320–334 (2013).
pmcid: 3760967
doi: 10.1016/j.cell.2013.03.036
pubmed: 23582323
Wang, Y. et al. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell 163, 174–186 (2015).
pmcid: 4583659
doi: 10.1016/j.cell.2015.08.063
pubmed: 26406377
Takayama, K. et al. Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. EMBO J. 32, 1665–1680 (2013).
pmcid: 3680743
doi: 10.1038/emboj.2013.99
pubmed: 23644382
Takayama, K., Suzuki, T., Fujimura, T., Takahashi, S. & Inoue, S. COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer. Proc. Natl Acad. Sci. USA 115, 4975–4980 (2018).
doi: 10.1073/pnas.1721957115
pubmed: 29686105
pmcid: 5948986
Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
pmcid: 2592715
doi: 10.1186/gb-2008-9-9-r137
pubmed: 18798982
Malik, R. et al. Targeting the MLL complex in castration-resistant prostate cancer. Nat. Med. 21, 344–352 (2015).
pmcid: 4390530
doi: 10.1038/nm.3830
pubmed: 25822367