|
|
|
Pioneer of prostate cancer: past, present and the future of FOXA1 |
Mona Teng1,2, Stanley Zhou1,2, Changmeng Cai3, Mathieu Lupien1,2,4( ), Housheng Hansen He1,2( ) |
1. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada 2. Department of Medical Biophysics, University of Toronto, Toronto, Canada 3. Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA 4. 4Ontario Institute for Cancer Research, Toronto, ON, Canada |
|
|
|
|
Abstract Prostate cancer is the most commonly diagnosed noncutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease. Forkhead box A1 (FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence and cis-regulatory elements (CREs) of FOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.
|
| Keywords
FOXA1
pioneer factor
transcription factor
prostate cancer
epigenetics
|
|
Corresponding Author(s):
Mathieu Lupien,Housheng Hansen He
|
|
Online First Date: 21 October 2020
Issue Date: 11 February 2021
|
|
| 1 |
EJ Adams, WR Karthaus, E Hoover, D Liu, A Gruet, Z Zhang, H Cho, R DiLoreto, S Chhangawala, Y Liuet al. (2019) FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature 571:408–412
https://doi.org/10.1038/s41586-019-1318-9
|
| 2 |
M Ahmed, RC Sallari, H Guo, JH Moore, HH He, M Lupien (2017) Variant Set Enrichment: an R package to identify diseaseassociated functional genomic regions. BioData Min 10:9
https://doi.org/10.1186/s13040-017-0129-5
|
| 3 |
American Cancer Society (2019) Cancer Facts & Figures 2019
|
| 4 |
M Annala, S Taavitsainen, G Vandekerkhove, JVW Bacon, K Beja, KN Chi, M Nykter, AW Wyatt (2018)Frequent mutation of the FOXA1 untranslated region in prostate cancer. Commun Biol 1:122
https://doi.org/10.1038/s42003-018-0128-1
|
| 5 |
CH Arrowsmith, C Bountra, PV Fish, K Lee, M Schapira (2012) Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 11:384–400
https://doi.org/10.1038/nrd3674
|
| 6 |
CE Barbieri, SC Baca, MS Lawrence, F Demichelis, M Blattner, J-P Theurillat, TA White, P Stojanov, E Van Allen, N Stranskyet al. (2012) Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44:685–689
https://doi.org/10.1038/ng.2279
|
| 7 |
H Beltran, D Prandi, JM Mosquera, M Benelli, L Puca, J Cyrta, C Marotz, E Giannopoulou, BVSK Chakravarthi, S Varamballyet al. (2016) Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med 22:298–305
https://doi.org/10.1038/nm.4045
|
| 8 |
H Beltran, A Romanel, V Conteduca, N Casiraghi, M Sigouros, GM Franceschini, F Orlando, T Fedrizzi, S-Y Ku, E Dannet al. (2020) Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. J Clin Invest 130:1653–1668
https://doi.org/10.1172/JCI131041
|
| 9 |
C Cai, HH He, S Gao, S Chen, Z Yu, Y Gao, S Chen, MW Chen, J Zhang, M Ahmedet al. (2014) Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity. Cell Rep 9:1618–1627
https://doi.org/10.1016/j.celrep.2014.11.008
|
| 10 |
Canadian Cancer Society (2019) Canadian Cancer Statistics 2019 Cancer Genome Atlas Research Network (2015) The Molecular Taxonomy of Primary Prostate Cancer. Cell 163:1011–1025
|
| 11 |
KL Clark, ED Halay, E Lai, SK Burley (1993) Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 364:412–420
https://doi.org/10.1038/364412a0
|
| 12 |
CV Dang, EP Reddy, KM Shokat, L Soucek (2017) Drugging the “undruggable” cancer targets. Nat Rev Cancer 17:502–508
https://doi.org/10.1038/nrc.2017.36
|
| 13 |
JR Dixon, DU Gorkin, B Ren (2016) Chromatin domains: the unit of chromosome organization. Mol Cell 62:668–680
https://doi.org/10.1016/j.molcel.2016.05.018
|
| 14 |
JR Dixon, S Selvaraj, F Yue, A Kim, Y Li, Y Shen, M Hu, JS Liu, B Ren (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–380
https://doi.org/10.1038/nature11082
|
| 15 |
SMG Espiritu, LY Liu, Y Rubanova, V Bhandari, EM Holgersen, LM Szyca, NS Fox, MLK Chua, TN Yamaguchi, LE Heisleret al. (2018) The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell 173:1003–1013.e15
https://doi.org/10.1016/j.cell.2018.03.029
|
| 16 |
Y Fang, G Liao, B Yu (2019) LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol 12:129
https://doi.org/10.1186/s13045-019-0811-9
|
| 17 |
S Farashi, T Kryza, J Clements, J Batra (2019) Post-GWAS in prostate cancer: from genetic association to biological contribution. Nat Rev Cancer 19:46–59
https://doi.org/10.1038/s41568-018-0087-3
|
| 18 |
M Fraser, VY Sabelnykova, TN Yamaguchi, LE Heisler, J Livingstone, V Huang, Y-J Shiah, F Yousif, X Lin, AP Masellaet al. (2017) Genomic hallmarks of localized, non-indolent prostate cancer. Nature 541:359–364
https://doi.org/10.1038/nature20788
|
| 19 |
N Gao, J Zhang, MA Rao, TC Case, J Mirosevich, Y Wang, R Jin, A Gupta, PS Rennie, RJ Matusik (2003) The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes. Mol Endocrinol 17:1484–1507
https://doi.org/10.1210/me.2003-0020
|
| 20 |
S Gao, S Chen, D Han, D Barrett, W Han, M Ahmed, S Patalano, JA Macoska, HH He, C Cai (2019) Forkhead domain mutations in FOXA1 drive prostate cancer progression. Cell Res 29:770–772
https://doi.org/10.1038/s41422-019-0203-2
|
| 21 |
S Gao, S Chen, D Han, Z Wang, M Li, W Han, A Besschetnova, M Liu, F Zhou, D Barrettet al. (2020) Chromatin binding of FOXA1 is promoted by LSD1-mediated demethylation in prostate cancer. Nat Genet.
https://doi.org/10.1038/s41588-020-0681-7
|
| 22 |
J Gerhardt, M Montani, P Wild, M Beer, F Huber, T Hermanns, M Müntener, G Kristiansen (2012) FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer. Am J Pathol 180:848–861
https://doi.org/10.1016/j.ajpath.2011.10.021
|
| 23 |
CS Grasso, Y-M Wu, DR Robinson, X Cao, SM Dhanasekaran, AP Khan, MJ Quist, X Jing, RJ Lonigro, JC Brenneret al. (2012) The mutational landscape of lethal castration-resistant prostate cancer. Nature 487:239–243
https://doi.org/10.1038/nature11125
|
| 24 |
GD Grossfeld, DM Latini, DP Lubeck, SS Mehta, PR Carroll (2003) Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer. J Urol 169:157–163
https://doi.org/10.1016/S0022-5347(05)64058-X
|
| 25 |
B Gui, F Gui, T Takai, C Feng, X Bai, L Fazli, X Dong, S Liu, X Zhang, W Zhanget al. (2019) Selective targeting of PARP-2 inhibits androgen receptor signaling and prostate cancer growth through disruption of FOXA1 function. Proceedings of the National Academy of Sciences 116:14573–14582
https://doi.org/10.1073/pnas.1908547116
|
| 26 |
W Hankey, Z Chen, Q Wang (2020) Shaping chromatin states in prostate cancer by pioneer transcription factors. Cancer Res.
https://doi.org/10.1158/0008-5472.CAN-19-3447
|
| 27 |
DJ Hazelett, SG Coetzee, GA Coetzee (2013) A rare variant, which destroys a FoxA1 site at 8q24, is associated with prostate cancer risk. Cell Cycle 12:379–380
https://doi.org/10.4161/cc.23201
|
| 28 |
FW Huang, JM Mosquera, A Garofalo, C Oh, M Baco, A Amin-Mansour, B Rabasha, S Bahl, SA Mullane, BD Robinsonet al. (2017) Exome sequencing of African-American prostate cancer reveals loss-of-function ERF mutations. Cancer Discov 7:973–983
https://doi.org/10.1158/2159-8290.CD-16-0960
|
| 29 |
J Huang, R Sengupta, AB Espejo, MG Lee, JA Dorsey, M Richter, S Opravil, R Shiekhattar, MT Bedford, T Jenuweinet al. (2007) p53 is regulated by the lysine demethylase LSD1. Nature 449:105–108
https://doi.org/10.1038/nature06092
|
| 30 |
M Iwafuchi, I Cuesta, G Donahue, N Takenaka, AB Osipovich, MA Magnuson, H Roder, SH Seeholzer, P Santisteban, KS Zaret (2020) Gene network transitions in embryos depend upon interactions between a pioneer transcription factor and core histones. Nat Genet 52:418–427
https://doi.org/10.1038/s41588-020-0591-8
|
| 31 |
H-J Jin, JC Zhao, I Ogden, RC Bergan, J Yu (2013) Androgen receptor-independent function of FoxA1 in prostate cancer metastasis. Cancer Res 73:3725–3736
https://doi.org/10.1158/0008-5472.CAN-12-3468
|
| 32 |
H-J Jin, JC Zhao, L Wu, J Kim, J Yu (2014) Cooperativity and equilibrium with FOXA1 define the androgen receptor transcriptional program. Nat Commun 5:3972
https://doi.org/10.1038/ncomms4972
|
| 33 |
J Kim, H Jin, JC Zhao, YA Yang, Y Li, X Yang, X Dong, J Yu (2017) FOXA1 inhibits prostate cancer neuroendocrine differentiation. Oncogene 36:4072–4080
https://doi.org/10.1038/onc.2017.50
|
| 34 |
S Kohler, LA Cirillo (2010) Stable chromatin binding prevents FoxA acetylation, preserving FoxA chromatin remodeling. J Biol Chem 285:464–472
https://doi.org/10.1074/jbc.M109.063149
|
| 35 |
J Li, C Xu, HJ Lee, S Ren, X Zi, Z Zhang, H Wang, Y Yu, C Yang, X Gaoet al. (2020) A genomic and epigenomic atlas of prostate cancer in Asian populations. Nature 580:93–99
https://doi.org/10.1038/s41586-020-2135-x
|
| 36 |
M Lupien, J Eeckhoute, CA Meyer, Q Wang, Y Zhang, W Li, JS Carroll, XS Liu, M Brown (2008) FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132:958–970
https://doi.org/10.1016/j.cell.2008.01.018
|
| 37 |
MT Maurano, R Humbert, E Rynes, RE Thurman, E Haugen, H Wang, AP Reynolds, R Sandstrom, H Qu, J Brodyet al. (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337:1190–1195
https://doi.org/10.1126/science.1222794
|
| 38 |
P Mazrooei, KJ Kron, Y Zhu, S Zhou, G Grillo, T Mehdi, M Ahmed, TM Severson, P Guilhamon, NS Armstronget al. (2019) Cistrome partitioning reveals convergence of somatic mutations and risk variants on master transcription regulators in primary prostate tumors. Cancer Cell 36:674–689.e6
https://doi.org/10.1016/j.ccell.2019.10.005
|
| 39 |
E Metzger, M Wissmann, N Yin, JM Müller, R Schneider, AHFM Peters, T Günther, R Buettner, R Schüle (2005) LSD1 demethylates repressive histone marks to promote androgen-receptordependent transcription. Nature 437:436–439
https://doi.org/10.1038/nature04020
|
| 40 |
S Müller, S Ackloo, CH Arrowsmith, M Bauser, JL Baryza, J Blagg, J Böttcher, C Bountra, PJ Brown, ME Bunnageet al. (2018) Science forum: donated chemical probes for open science. Elife 7:e34311
https://doi.org/10.7554/eLife.34311
|
| 41 |
EP Nora, BR Lajoie, EG Schulz, L Giorgetti, I Okamoto, N Servant, T Piolot, NL van Berkum, J Meisig, J Sedatet al. (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–385
https://doi.org/10.1038/nature11049
|
| 42 |
A Parolia, M Cieslik, S-C Chu, L Xiao, T Ouchi, Y Zhang, X Wang, P Vats, X Cao, S Pitchiayaet al. (2019) Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer. Nature 571:413–418
https://doi.org/10.1038/s41586-019-1347-4
|
| 43 |
MM Pomerantz, F Li, DY Takeda, R Lenci, A Chonkar, M Chabot, P Cejas, F Vazquez, J Cook, RA Shivdasaniet al. (2015) The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis. Nat Genet 47:1346–1351
https://doi.org/10.1038/ng.3419
|
| 44 |
MM Pomerantz, X Qiu, Y Zhu, DY Takeda, W Pan, SC Baca, A Gusev, KD Korthauer, TM Severson, G Haet al. (2020) Prostate cancer reactivates developmental epigenomic programs during metastatic progression. Nat Genet 52:790–799
https://doi.org/10.1038/s41588-020-0664-8
|
| 45 |
DA Quigley, HX Dang, SG Zhao, P Lloyd, R Aggarwal, JJ Alumkal, A Foye, V Kothari, MD Perry, AM Baileyet al. (2018) Genomic hallmarks and structural variation in metastatic prostate cancer. Cell 174:758–769.e9
|
| 46 |
M Rotinen, S You, J Yang, SG Coetzee, M Reis-Sobreiro, W-C Huang, F Huang, X Pan, A Yáñez , DJ Hazelettet al. (2018) ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis. Nat Med 24:1887–1898
https://doi.org/10.1038/s41591-018-0241-1
|
| 47 |
R Sabarinathan, L Mularoni, J Deu-Pons, A Gonzalez-Perez, N López-Bigas (2016) Nucleotide excision repair is impaired by binding of transcription factors to DNA. Nature 532:264–267
https://doi.org/10.1038/nature17661
|
| 48 |
B Sahu, M Laakso, K Ovaska, T Mirtti, J Lundin, A Rannikko, A Sankila, J-P Turunen, M Lundin, J Konstiet al. (2011) Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer. EMBO J 30:3962–3976
https://doi.org/10.1038/emboj.2011.328
|
| 49 |
B Sahu, M Laakso, P Pihlajamaa, K Ovaska, I Sinielnikov, S Hautaniemi, OA Jänne (2013) FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells. Cancer Res 73:1570–1580
https://doi.org/10.1158/0008-5472.CAN-12-2350
|
| 50 |
S Scheer, S Ackloo, TS Medina, M Schapira, F Li, JA Ward, AM Lewis, JP Northrop, PL Richardson, HÜ Kaniskanet al. (2019) A chemical biology toolbox to study protein methyltransferases and epigenetic signaling. Nat Commun 10:19
https://doi.org/10.1038/s41467-018-07905-4
|
| 51 |
A Sehrawat, L Gao, Y Wang, A 3rd Bankhead, SK McWeeney, CJ King, J Schwartzman, J Urrutia, WH Bisson, DJ Colemanet al. (2018) LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci USA 115:E4179–E4188
https://doi.org/10.1158/1538-7445.AM2018-LB-240
|
| 52 |
T Sekiya, UM Muthurajan, K Luger, AV Tulin, KS Zaret (2009) Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. Genes Dev 23:804–809
https://doi.org/10.1101/gad.1775509
|
| 53 |
AA Sérandour, S Avner, F Percevault, F Demay, M Bizot, C Lucchetti-Miganeh, F Barloy-Hubler, M Brown, M Lupien, R Métivieret al. (2011) Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res 21:555–565
https://doi.org/10.1101/gr.111534.110
|
| 54 |
Y Shi, F Lan, C Matson, P Mulligan, JR Whetstine, PA Cole, RA Casero, Y Shi (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953
https://doi.org/10.1016/j.cell.2004.12.012
|
| 55 |
B Song, S-H Park, JC Zhao, K-W Fong, S Li, Y Lee, YA Yang, S Sridhar, X Lu, SA Abdulkadiret al. (2019) Targeting FOXA1-mediated repression of TGF-β signaling suppresses castrationresistant prostate cancer progression. J Clin Invest 129:569–582
https://doi.org/10.1172/JCI122367
|
| 56 |
P Sutinen, V Rahkama, M Rytinki, JJ Palvimo (2014) Nuclear mobility and activity of FOXA1 with androgen receptor are regulated by SUMOylation. Mol Endocrinol 28:1719–1728
https://doi.org/10.1210/me.2014-1035
|
| 57 |
Q Szabo, F Bantignies, G Cavalli (2019) Principles of genome folding into topologically associating domains. Sci Adv 5: eaaw1668
https://doi.org/10.1126/sciadv.aaw1668
|
| 58 |
D Wang, I Garcia-Bassets, C Benner, W Li, X Su, Y Zhou, J Qiu, W Liu, MU Kaikkonen, KA Ohgiet al. (2011) Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474:390–394
https://doi.org/10.1038/nature10006
|
| 59 |
J Wang, S Hevi, JK Kurash, H Lei, F Gay, J Bajko, H Su, W Sun, H Chang, G Xuet al.(2009a) The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet 41:125–129
https://doi.org/10.1038/ng.268
|
| 60 |
Q Wang, W Li, Y Zhang, X Yuan, K Xu, J Yu, Z Chen, R Beroukhim, H Wang, M Lupienet al. (2009b) Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell 138:245–256
https://doi.org/10.1016/j.cell.2009.04.056
|
| 61 |
S Wang, S Singh, M Katika, S Lopez-Aviles, A Hurtado (2018) High throughput chemical screening reveals multiple regulatory proteins on FOXA1 in breast cancer cell lines. International Journal of Molecular Sciences 19:4123
https://doi.org/10.3390/ijms19124123
|
| 62 |
PA Watson, VK Arora, CL Sawyers (2015) Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 15:701–711
https://doi.org/10.1038/nrc4016
|
| 63 |
T Whitington, P Gao, W Song, H Ross-Adams, AD Lamb, Y Yang, I Svezia, D Klevebring, IG Mills, R Karlssonet al. (2016) Gene regulatory mechanisms underpinning prostate cancer susceptibility. Nat Genet 48:387–397
https://doi.org/10.1038/ng.3523
|
| 64 |
M Wissmann, N Yin, JM Müller, H Greschik, BD Fodor, T Jenuwein, C Vogler, R Schneider, T Günther, R Buettneret al. (2007) Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol 9:347–353
https://doi.org/10.1038/ncb1546
|
| 65 |
Q Wu, D Heidenreich, S Zhou, S Ackloo, A Krämer, K Nakka, E Lima-Fernandes, G Deblois, S Duan, RN Vellankiet al. (2019) A chemical toolbox for the study of bromodomains and epigenetic signaling. Nat Commun 10:1915
https://doi.org/10.1038/s41467-019-09672-2
|
| 66 |
B Xu, B Song, X Lu, J Kim, M Hu, JC Zhao, J Yu (2019) Altered chromatin recruitment by FOXA1 mutations promotes androgen independence and prostate cancer progression. Cell Res 29:773–775
https://doi.org/10.1038/s41422-019-0204-1
|
| 67 |
N Yamaguchi, M Shibazaki, C Yamada, E Anzai, M Morii, Y Nakayama, T Kuga, Y Hashimoto, T Tomonaga, N Yamaguchi (2017) Tyrosine phosphorylation of the pioneer transcription factor FoxA1 promotes activation of estrogen signaling. J Cell Biochem 118:1453–1461
https://doi.org/10.1002/jcb.25804
|
| 68 |
X Zhang, SD Bailey, M Lupien (2014) Laying a solid foundation for Manhattan–’setting the functional basis for the post-GWAS era’. Trends Genet 30:140–149
https://doi.org/10.1016/j.tig.2014.02.006
|
| 69 |
X Zhang, R Cowper-Sal-lari, SD Bailey, JH Moore, M Lupien (2012) Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus. Genome Research 22:1437–1446
https://doi.org/10.1101/gr.135665.111
|
| 70 |
S Zhou, JR Hawley, F Soares, G Grillo, M Teng, SA Madani Tonekaboni, JT Hua, KJ Kron, P Mazrooei, M Ahmedet al. (2020) Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer. Nat Commun 11:441
https://doi.org/10.1038/s41467-020-14318-9
|
| 71 |
S Zhou, AE Treloar, M Lupien (2016) Emergence of the Noncoding Cancer Genome: A Target of Genetic and Epigenetic Alterations. Cancer Discov 6:1215–1229
https://doi.org/10.1158/2159-8290.CD-16-0745
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|