The diverse roles of SPOP in prostate cancer and kidney cancer.
Journal
Nature reviews. Urology
ISSN: 1759-4820
Titre abrégé: Nat Rev Urol
Pays: England
ID NLM: 101500082
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
accepted:
25
03
2020
pubmed:
2
5
2020
medline:
21
1
2022
entrez:
2
5
2020
Statut:
ppublish
Résumé
Multiple studies have confirmed that speckle-type pox virus and zinc finger (POZ) protein (SPOP) functions as a substrate adaptor of cullin 3-based E3 ligase and has a crucial role in various cellular processes via specific targeting of proteins for ubiquitination and subsequent proteasomal degradation. Dysregulation of SPOP-mediated proteolysis might be involved in the development and progression of human prostate and kidney cancers. In prostate cancer, SPOP seems to function as a tumour suppressor by targeting several proteins, including androgen receptor (AR), steroid receptor coactivator 3 (SRC3) and BRD4, for degradation, whereas it might function as an oncoprotein in kidney cancer, for example, by targeting phosphatase and tensin homologue (PTEN) for proteasomal degradation. In addition, nuclear SPOP targets AR for degradation and has a role as a tumour suppressor in prostate cancer; however, in kidney cancer, SPOP largely accumulates in the cytoplasm and fails to promote degradation of AR located in the nucleus, resulting in activation of AR-driven pathways and cancer progression. Owing to the context-dependent function of SPOP in human malignancies, further assessment of the molecular mechanisms involving SPOP in prostate and kidney cancers is needed to improve our understanding of its role in the development of these cancer types. Treatments that target SPOP might become therapeutic strategies in these malignancies in the future.
Identifiants
pubmed: 32355326
doi: 10.1038/s41585-020-0314-z
pii: 10.1038/s41585-020-0314-z
doi:
Substances chimiques
Nuclear Proteins
0
Repressor Proteins
0
SPOP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
339-350Références
Wei, X. et al. Functional roles of speckle-type Poz (SPOP) protein in genomic stability. J. Cancer 9, 3257–3262 (2018).
pubmed: 30271484
pmcid: 6160670
Stone, L. Kidney cancer: on target - inhibiting SPOP in ccRCC. Nat. Rev. Urol. 13, 630 (2016).
pubmed: 27698399
Ciechanover, A. The unravelling of the ubiquitin system. Nat. Rev. Mol. Cell Biol. 16, 322–324 (2015).
pubmed: 25907614
Nakayama, K. I. & Nakayama, K. Ubiquitin ligases: cell-cycle control and cancer. Nat. Rev. Cancer 6, 369–381 (2006).
pubmed: 16633365
Hershko, A., Heller, H., Elias, S. & Ciechanover, A. Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J. Biol. Chem. 258, 8206–8214 (1983).
pubmed: 6305978
Schulman, B. A. & Harper, J. W. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol. 10, 319–331 (2009).
pubmed: 19352404
pmcid: 2712597
Natarajan, C. & Takeda, K. Regulation of various DNA repair pathways by E3 ubiquitin ligases. J. Cancer Res. Ther. 13, 157–169 (2017).
pubmed: 28643728
O’Connor, H. F. & Huibregtse, J. M. Enzyme-substrate relationships in the ubiquitin system: approaches for identifying substrates of ubiquitin ligases. Cell Mol. Life Sci. 74, 3363–3375 (2017).
pubmed: 28455558
pmcid: 5545068
Liu, J. et al. Targeting the ubiquitin pathway for cancer treatment. Biochim. Biophys. Acta 1855, 50–60 (2015).
pubmed: 25481052
Buetow, L. & Huang, D. T. Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Nat. Rev. Mol. Cell Biol. 17, 626–642 (2016).
pubmed: 27485899
pmcid: 6211636
Zheng, N. & Shabek, N. Ubiquitin ligases: structure, function, and regulation. Annu. Rev. Biochem. 86, 129–157 (2017).
pubmed: 28375744
Genschik, P., Sumara, I. & Lechner, E. The emerging family of CULLIN3-RING ubiquitin ligases (CRL3s): cellular functions and disease implications. EMBO J. 32, 2307–2320 (2013).
pubmed: 23912815
pmcid: 3770339
Hernandez-Munoz, I. et al. Stable X chromosome inactivation involves the PRC1 polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc. Natl Acad. Sci. USA 102, 7635–7640 (2005).
pubmed: 15897469
Cheng, J. et al. Functional analysis of Cullin 3 E3 ligases in tumorigenesis. Biochim. Biophys. Acta Rev. Cancer 1869, 11–28 (2018).
pubmed: 29128526
Singer, J. D., Gurian-West, M., Clurman, B. & Roberts, J. M. Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. Genes Dev. 13, 2375–2387 (1999).
pubmed: 10500095
pmcid: 317026
Kossatz, U. et al. The cyclin E regulator cullin 3 prevents mouse hepatic progenitor cells from becoming tumor-initiating cells. J. Clin. Invest. 120, 3820–3833 (2010).
pubmed: 20978349
pmcid: 2964969
McCormick, J. A. et al. Hyperkalemic hypertension-associated cullin 3 promotes WNK signaling by degrading KLHL3. J. Clin. Invest. 124, 4723–4736 (2014).
pubmed: 25250572
pmcid: 4347254
Mathew, R. et al. BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs. Nature 491, 618–621 (2012).
pubmed: 23086144
pmcid: 3504649
Liu, J. et al. Analysis of Drosophila segmentation network identifies a JNK pathway factor overexpressed in kidney cancer. Science 323, 1218–1222 (2009).
pubmed: 19164706
pmcid: 2756524
Brenner, J. C. & Chinnaiyan, A. M. Disruptive events in the life of prostate cancer. Cancer Cell 19, 301–303 (2011).
pubmed: 21397854
Nagai, Y. et al. Identification of a novel nuclear speckle-type protein, SPOP. FEBS Lett. 418, 23–26 (1997).
pubmed: 9414087
Zhuang, M. et al. Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol. Cell 36, 39–50 (2009).
pubmed: 19818708
pmcid: 2847577
Li, G. et al. SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer. Cancer Cell 25, 455–468 (2014).
pubmed: 24656772
pmcid: 4443692
Barbieri, C. E. et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat. Genet. 44, 685–689 (2012).
pubmed: 22610119
pmcid: 3673022
Le Gallo, M. et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat. Genet. 44, 1310–1315 (2012).
pubmed: 23104009
pmcid: 3515204
Kim, M. S., Je, E. M., Oh, J. E., Yoo, N. J. & Lee, S. H. Mutational and expressional analyses of SPOP, a candidate tumor suppressor gene, in prostate, gastric and colorectal cancers. APMIS 121, 626–633 (2013).
pubmed: 23216165
Yoo, S. K. et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet. 12, e1006239 (2016).
pubmed: 27494611
pmcid: 4975456
Kan, Z. et al. Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466, 869–873 (2010).
pubmed: 20668451
Chong, P. A. & Forman-Kay, J. D. Liquid-liquid phase separation in cellular signaling systems. Curr. Opin. Struct. Biol. 41, 180–186 (2016).
pubmed: 27552079
Bouchard, J. J. et al. Cancer mutations of the tumor suppressor SPOP disrupt the formation of active, phase-separated compartments. Mol. Cell 72, 19–36.e8 (2018).
pubmed: 30244836
pmcid: 6179159
Richards, E. J. Inherited epigenetic variation–revisiting soft inheritance. Nat. Rev. Genet. 7, 395–401 (2006).
pubmed: 16534512
Zhi, X. et al. Silencing speckle-type POZ protein by promoter hypermethylation decreases cell apoptosis through upregulating Hedgehog signaling pathway in colorectal cancer. Cell Death Dis. 7, e2569 (2016).
pubmed: 28032859
pmcid: 5261007
Huang, C. J., Chen, H. Y., Lin, W. Y. & Choo, K. B. Differential expression of speckled POZ protein, SPOP: putative regulation by miR-145. J. Biosci. 39, 401–413 (2014).
pubmed: 24845504
Xu, J., Wang, F., Wang, X., He, Z. & Zhu, X. miRNA-543 promotes cell migration and invasion by targeting SPOP in gastric cancer. Onco Targets Ther. 11, 5075–5082 (2018).
pubmed: 30174445
pmcid: 6110661
Ding, M. et al. The E2F1-miR-520/372/373-SPOP axis modulates progression of renal carcinoma. Cancer Res. 78, 6771–6784 (2018).
pubmed: 30348808
LaGory, E. L. & Giaccia, A. J. The ever-expanding role of HIF in tumour and stromal biology. Nat. Cell Biol. 18, 356–365 (2016).
pubmed: 27027486
pmcid: 4898054
Guo, Z. Q. et al. Small-molecule targeting of E3 ligase adaptor SPOP in kidney cancer. Cancer Cell 30, 474–484 (2016).
pubmed: 27622336
An, J., Wang, C., Deng, Y., Yu, L. & Huang, H. Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell Rep. 6, 657–669 (2014).
pubmed: 24508459
pmcid: 4361392
Lai, J. & Batra, J. Speckle-type POZ protein mutations interrupt tumor suppressor function of speckle-type POZ protein in prostate cancer by affecting androgen receptor degradation. Asian J. Androl. 16, 659–660 (2014).
pubmed: 24969063
pmcid: 4215653
Geng, C. et al. Androgen receptor is the key transcriptional mediator of the tumor suppressor SPOP in prostate cancer. Cancer Res. 74, 5631–5643 (2014).
pubmed: 25274033
pmcid: 4209379
Dai, X. et al. Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4. Nat. Med. 23, 1063–1071 (2017).
pubmed: 28805820
pmcid: 5625299
Janouskova, H. et al. Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors. Nat. Med. 23, 1046–1054 (2017).
pubmed: 28805821
pmcid: 5592092
Zhang, P. et al. Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation. Nat. Med. 23, 1055–1062 (2017).
pubmed: 28805822
pmcid: 5653288
Wu, F. et al. Prostate cancer-associated mutation in SPOP impairs its ability to target Cdc20 for poly-ubiquitination and degradation. Cancer Lett. 385, 207–214 (2017).
pubmed: 27780719
Geng, C. et al. SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination and turnover of c-MYC oncoprotein. Oncogene 36, 4767–4777 (2017).
pubmed: 28414305
pmcid: 5887163
An, J. et al. Truncated ERG oncoproteins from TMPRSS2-ERG fusions are resistant to SPOP-mediated proteasome degradation. Mol. Cell 59, 904–916 (2015).
pubmed: 26344096
Duan, S. & Pagano, M. SPOP mutations or ERG rearrangements result in enhanced levels of ERG to promote cell invasion in prostate cancer. Mol. Cell 59, 883–884 (2015).
pubmed: 26384661
pmcid: 4948578
Gan, W. et al. SPOP promotes ubiquitination and degradation of the ERG oncoprotein to suppress prostate cancer progression. Mol. Cell 59, 917–930 (2015).
pubmed: 26344095
pmcid: 4575912
Geng, C. et al. Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate steroid receptor coactivator 3 protein turnover. Proc. Natl Acad. Sci. USA 110, 6997–7002 (2013).
pubmed: 23559371
Berger, M. F. et al. The genomic complexity of primary human prostate cancer. Nature 470, 214–220 (2011).
pubmed: 21307934
pmcid: 3075885
Blattner, M. et al. SPOP mutations in prostate cancer across demographically diverse patient cohorts. Neoplasia 16, 14–20 (2014).
pubmed: 24563616
pmcid: 3924544
Boysen, G. et al. SPOP-mutated/CHD1-deleted lethal prostate cancer and abiraterone sensitivity. Clin. Cancer Res. 24, 5585–5593 (2018).
pubmed: 30068710
pmcid: 6830304
Lee, D. et al. Molecular alterations in prostate cancer and association with MRI features. Prostate Cancer Prostatic Dis. 20, 430–435 (2017).
pubmed: 28762374
Bottcher, R. et al. Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations. BMC Cancer 18, 8 (2018).
pubmed: 29295717
pmcid: 5751811
Beltran, H. et al. Impact of therapy on genomics and transcriptomics in high-risk prostate cancer treated with neoadjuvant docetaxel and androgen deprivation therapy. Clin. Cancer Res. 23, 6802–6811 (2017).
pubmed: 28842510
pmcid: 5690882
Nguyen, H. M. et al. LuCaP prostate cancer patient-derived xenografts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics. Prostate 77, 654–671 (2017).
pubmed: 28156002
pmcid: 5354949
Spans, L. et al. Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1. Oncotarget 7, 24326–24338 (2016).
pubmed: 27014907
pmcid: 5029704
Manson-Bahr, D. et al. Mutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing. J. Clin. Pathol. 68, 212–217 (2015).
pubmed: 25586381
Rubin, M. A. & Demichelis, F. The genomics of prostate cancer: emerging understanding with technologic advances. Mod. Pathol. 31, S1–S11 (2018).
pubmed: 29297493
Zuhlke, K. A. et al. Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer. Prostate 74, 983–990 (2014).
pubmed: 24796539
pmcid: 4230298
Buckles, E. et al. Identification of speckle-type POZ protein somatic mutations in African American prostate cancer. Asian J. Androl. 16, 829–832 (2014).
pubmed: 24994784
pmcid: 4236324
Khani, F. et al. Evidence for molecular differences in prostate cancer between African American and Caucasian men. Clin. Cancer Res. 20, 4925–4934 (2014).
pubmed: 25056375
pmcid: 4167562
Vinceneux, A. et al. Ductal adenocarcinoma of the prostate: clinical and biological profiles. Prostate 77, 1242–1250 (2017).
pubmed: 28699202
Wang, H. et al. Quantification of mutant SPOP proteins in prostate cancer using mass spectrometry-based targeted proteomics. J. Transl Med. 15, 175 (2017).
pubmed: 28810879
pmcid: 5557563
Romanel, A. et al. Inherited determinants of early recurrent somatic mutations in prostate cancer. Nat. Commun. 8, 48 (2017).
pubmed: 28663546
pmcid: 5491529
Tan, S. H., Petrovics, G. & Srivastava, S. Prostate cancer genomics: recent advances and the prevailing underrepresentation from racial and ethnic minorities. Int. J. Mol. Sci. 19, E1255 (2018).
Jung, S. H. et al. Genetic progression of high grade prostatic intraepithelial neoplasia to prostate cancer. Eur. Urol. 69, 823–830 (2016).
pubmed: 26542946
Hjorth-Jensen, K. et al. SPOP promotes transcriptional expression of DNA repair and replication factors to prevent replication stress and genomic instability. Nucleic Acids Res. 46, 9484–9495 (2018).
pubmed: 30124983
pmcid: 6182143
Boysen, G. et al. SPOP mutation leads to genomic instability in prostate cancer. Elife 4, e09207 (2015).
pubmed: 26374986
pmcid: 4621745
Zhang, D. et al. Speckle-type POZ protein, SPOP, is involved in the DNA damage response. Carcinogenesis 35, 1691–1697 (2014).
pubmed: 24451148
pmcid: 4123640
Claiborn, K. C. et al. Pcif1 modulates Pdx1 protein stability and pancreatic beta cell function and survival in mice. J. Clin. Invest. 120, 3713–3721 (2010).
pubmed: 20811152
pmcid: 2947215
Blattner, M. et al. SPOP mutation drives prostate tumorigenesis in vivo through coordinate regulation of PI3K/mTOR and AR signaling. Cancer Cell 31, 436–451 (2017).
pubmed: 28292441
pmcid: 5384998
Garcia-Flores, M. et al. Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer. Eur. J. Cancer 50, 2994–3002 (2014).
pubmed: 25204806
Loh, S. N. Follow the mutations: toward class-specific, small-molecule reactivation of p53. Biomolecules 10, 303 (2020).
pmcid: 7072143
Lopez-Bergami, P., Lau, E. & Ronai, Z. Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat. Rev. Cancer 10, 65–76 (2010).
pubmed: 20029425
pmcid: 2874064
Maekawa, T. et al. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 8, 2023–2028 (1989).
pubmed: 2529117
pmcid: 401081
Vlahopoulos, S. A. et al. The role of ATF-2 in oncogenesis. Bioessays 30, 314–327 (2008).
pubmed: 18348191
Ricote, M. et al. The p38 transduction pathway in prostatic neoplasia. J. Pathol. 208, 401–407 (2006).
pubmed: 16369914
Zhang, S., Dong, X., Ji, T., Chen, G. & Shan, L. Long non-coding RNA UCA1 promotes cell progression by acting as a competing endogenous RNA of ATF2 in prostate cancer. Am. J. Transl Res. 9, 366–375 (2017).
pubmed: 28337266
pmcid: 5340673
Ma, J. et al. SPOP promotes ATF2 ubiquitination and degradation to suppress prostate cancer progression. J. Exp. Clin. Cancer Res. 37, 145 (2018).
pubmed: 29996942
pmcid: 6042370
Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010).
pubmed: 20871596
pmcid: 3010259
Belkina, A. C. & Denis, G. V. BET domain co-regulators in obesity, inflammation and cancer. Nat. Rev. Cancer 12, 465–477 (2012).
pubmed: 22722403
pmcid: 3934568
Jang, M. K. et al. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol. Cell 19, 523–534 (2005).
pubmed: 16109376
Shi, J. & Vakoc, C. R. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol. Cell 54, 728–736 (2014).
pubmed: 24905006
Delmore, J. E. et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146, 904–917 (2011).
pubmed: 21889194
pmcid: 3187920
Mertz, J. A. et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc. Natl Acad. Sci. USA 108, 16669–16674 (2011).
pubmed: 21949397
Shi, J. et al. Disrupting the interaction of BRD4 with diacetylated twist suppresses tumorigenesis in basal-like breast cancer. Cancer Cell 25, 210–225 (2014).
pubmed: 24525235
pmcid: 4004960
Asangani, I. A. et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature 510, 278–282 (2014).
pubmed: 24759320
pmcid: 4075966
Li, X. et al. BRD4 promotes DNA repair and mediates the formation of TMPRSS2-ERG gene rearrangements in prostate cancer. Cell Rep. 22, 796–808 (2018).
pubmed: 29346775
pmcid: 5843368
Crawford, N. P. et al. Bromodomain 4 activation predicts breast cancer survival. Proc. Natl Acad. Sci. USA 105, 6380–6385 (2008).
pubmed: 18427120
Dai, X., Wang, Z. & Wei, W. SPOP-mediated degradation of BRD4 dictates cellular sensitivity to BET inhibitors. Cell Cycle 16, 2326–2329 (2017).
pubmed: 29108467
pmcid: 5788415
Jin, X. et al. DUB3 promotes BET inhibitor resistance and cancer progression by deubiquitinating BRD4. Mol. Cell 71, 592–605 e4 (2018).
pubmed: 30057199
pmcid: 6086352
Yu, H. Cdc20: a WD40 activator for a cell cycle degradation machine. Mol. Cell 27, 3–16 (2007).
pubmed: 17612486
Kidokoro, T. et al. CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene 27, 1562–1571 (2008).
pubmed: 17873905
Wang, L. et al. Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol. Ther. 151, 141–151 (2015).
pubmed: 25850036
pmcid: 4457591
Karra, H. et al. Cdc20 and securin overexpression predict short-term breast cancer survival. Br. J. Cancer 110, 2905–2913 (2014).
pubmed: 24853182
pmcid: 4056061
Ding, Z. Y., Wu, H. R., Zhang, J. M., Huang, G. R. & Ji, D. D. Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int. J. Clin. Exp. Pathol. 7, 722–727 (2014).
pubmed: 24551295
pmcid: 3925919
Gayyed, M. F., El-Maqsoud, N. M., Tawfiek, E. R., El Gelany, S. A. & Rahman, M. F. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage. Tumour Biol. 37, 749–762 (2016).
pubmed: 26245990
Mao, Y. et al. Overexpression of Cdc20 in clinically localized prostate cancer: relation to high Gleason score and biochemical recurrence after laparoscopic radical prostatectomy. Cancer Biomark. 16, 351–358 (2016).
pubmed: 26889981
Manchado, E. et al. Targeting mitotic exit leads to tumor regression in vivo: modulation by Cdk1, mastl, and the PP2A/B55α,δ phosphatase. Cancer Cell 18, 641–654 (2010).
pubmed: 21156286
Huang, H. C., Shi, J., Orth, J. D. & Mitchison, T. J. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell 16, 347–358 (2009).
pubmed: 19800579
pmcid: 2758291
Li, K. et al. Silencing of CDC20 suppresses metastatic castration-resistant prostate cancer growth and enhances chemosensitivity to docetaxel. Int. J. Oncol. 49, 1679–1685 (2016).
pubmed: 27633058
Dang, C. V. MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb. Perspect. Med. 3, a014217 (2013).
pubmed: 23906881
pmcid: 3721271
Fleming, W. H. et al. Expression of the c-myc protooncogene in human prostatic carcinoma and benign prostatic hyperplasia. Cancer Res. 46, 1535–1538 (1986).
pubmed: 2417706
Gurel, B. et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod. Pathol. 21, 1156–1167 (2008).
pubmed: 18567993
pmcid: 3170853
Antonarakis, E. S. et al. An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. Cancer 118, 6063–6071 (2012).
pubmed: 22674438
pmcid: 3572534
Hawksworth, D. et al. Overexpression of C-MYC oncogene in prostate cancer predicts biochemical recurrence. Prostate Cancer Prostatic Dis. 13, 311–315 (2010).
pubmed: 20820186
Vander Griend, D. J., Litvinov, I. V. & Isaacs, J. T. Conversion of androgen receptor signaling from a growth suppressor in normal prostate epithelial cells to an oncogene in prostate cancer cells involves a gain of function in c-Myc regulation. Int. J. Biol. Sci. 10, 627–642 (2014).
Antony, L., van der Schoor, F., Dalrymple, S. L. & Isaacs, J. T. Androgen receptor (AR) suppresses normal human prostate epithelial cell proliferation via AR/β-catenin/TCF-4 complex inhibition of c-MYC transcription. Prostate 74, 1118–1131 (2014).
pubmed: 24913829
pmcid: 4856018
Bernard, D., Pourtier-Manzanedo, A., Gil, J. & Beach, D. H. Myc confers androgen-independent prostate cancer cell growth. J. Clin. Invest. 112, 1724–1731 (2003).
pubmed: 14660748
pmcid: 281646
Zafarana, G. et al. Copy number alterations of c-MYC and PTEN are prognostic factors for relapse after prostate cancer radiotherapy. Cancer 118, 4053–4062 (2012).
pubmed: 22281794
Siu, K. T., Rosner, M. R. & Minella, A. C. An integrated view of cyclin E function and regulation. Cell Cycle 11, 57–64 (2012).
pubmed: 22186781
pmcid: 3272232
Koepp, D. M. et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294, 173–177 (2001).
pubmed: 11533444
Welcker, M. & Clurman, B. E. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat. Rev. Cancer 8, 83–93 (2008).
pubmed: 18094723
Tan, Y., Sangfelt, O. & Spruck, C. The Fbxw7/hCdc4 tumor suppressor in human cancer. Cancer Lett. 271, 1–12 (2008).
pubmed: 18541364
Spruck, C. H., Won, K. A. & Reed, S. I. Deregulated cyclin E induces chromosome instability. Nature 401, 297–300 (1999).
pubmed: 10499591
Loeb, K. R. et al. A mouse model for cyclin E-dependent genetic instability and tumorigenesis. Cancer Cell 8, 35–47 (2005).
pubmed: 16023597
Hwang, H. C. & Clurman, B. E. Cyclin E in normal and neoplastic cell cycles. Oncogene 24, 2776–2786 (2005).
pubmed: 15838514
Resnitzky, D., Gossen, M., Bujard, H. & Reed, S. I. Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. Mol. Cell Biol. 14, 1669–1679 (1994).
pubmed: 8114703
pmcid: 358525
Bortner, D. M. & Rosenberg, M. P. Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol. Cell Biol. 17, 453–459 (1997).
pubmed: 8972226
pmcid: 231770
Keyomarsi, K. et al. Cyclin E and survival in patients with breast cancer. N. Engl. J. Med. 347, 1566–1575 (2002).
pubmed: 12432043
Pils, D. et al. Cyclin E1 (CCNE1) as independent positive prognostic factor in advanced stage serous ovarian cancer patients – a study of the OVCAD consortium. Eur. J. Cancer 50, 99–110 (2014).
pubmed: 24176298
Ju, L. G. et al. SPOP suppresses prostate cancer through regulation of CYCLIN E1 stability. Cell Death Differ. 26, 1156–1168 (2019).
pubmed: 30237511
Sanden, C. & Gullberg, U. The DEK oncoprotein and its emerging roles in gene regulation. Leukemia 29, 1632–1636 (2015).
pubmed: 25765544
Teng, Y., Lang, L. & Jauregui, C. E. The complexity of DEK signaling in cancer progression. Curr. Cancer Drug Targets 18, 256–265 (2018).
pubmed: 28530531
Lin, D. et al. Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer. Oncotarget 6, 1806–1820 (2015).
pubmed: 25544761
Theurillat, J. P. et al. Prostate cancer. Ubiquitylome analysis identifies dysregulation of effector substrates in SPOP-mutant prostate cancer. Science 346, 85–89 (2014).
pubmed: 25278611
pmcid: 4257137
Zhang, Q. et al. Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell 16, 413–424 (2009).
pubmed: 19878873
pmcid: 2788761
Zheng, X. et al. Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Genes. Dev. 28, 1429–1444 (2014).
pubmed: 24990963
pmcid: 4083087
Henze, A. T. et al. Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback regulators of hypoxia-inducible factors. Cancer Res. 70, 357–366 (2010).
pubmed: 20028863
Briggs, K. J. et al. Paracrine induction of HIF by glutamate in breast cancer: EglN1 senses cysteine. Cell 166, 126–139 (2016).
pubmed: 27368101
pmcid: 4930557
Deschoemaeker, S. et al. PHD1 regulates p53-mediated colorectal cancer chemoresistance. EMBO Mol. Med. 7, 1350–1365 (2015).
pubmed: 26290450
pmcid: 4604688
Zhang, L. et al. Tumor suppressor SPOP ubiquitinates and degrades EglN2 to compromise growth of prostate cancer cells. Cancer Lett. 390, 11–20 (2017).
pubmed: 28089830
pmcid: 5511705
Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644–648 (2005).
pubmed: 16254181
Yang, Y. et al. Loss of FOXO1 cooperates with TMPRSS2-ERG overexpression to promote prostate tumorigenesis and cell invasion. Cancer Res. 77, 6524–6537 (2017).
pubmed: 28986382
pmcid: 5712249
Lin, B. et al. Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 59, 4180–4184 (1999).
pubmed: 10485450
Nam, R. K. et al. Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br. J. Cancer 97, 1690–1695 (2007).
pubmed: 17971772
pmcid: 2360284
Seth, A. & Watson, D. K. ETS transcription factors and their emerging roles in human cancer. Eur. J. Cancer 41, 2462–2478 (2005).
pubmed: 16213704
Shoag, J. et al. SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG. J. Clin. Invest. 128, 381–386 (2018).
pubmed: 29202479
Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568–571 (2014).
pubmed: 25428505
pmcid: 4246418
Bonfiglio, R. et al. PD-L1 in immune-escape of breast and prostate cancers: from biology to therapy. Future Oncol. 13, 2129–2131 (2017).
pubmed: 28984478
Keir, M. E., Butte, M. J., Freeman, G. J. & Sharpe, A. H. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 26, 677–704 (2008).
pubmed: 18173375
Sunshine, J. & Taube, J. M. PD-1/PD-L1 inhibitors. Curr. Opin. Pharmacol. 23, 32–38 (2015).
pubmed: 26047524
pmcid: 4516625
Gridelli, C. et al. The evolving role of nivolumab in non-small-cell lung cancer for second-line treatment: a new cornerstone for our treatment algorithms. Results from an international experts panel meeting of the Italian Association of Thoracic Oncology. Clin. Lung Cancer 17, 161–168 (2016).
pubmed: 26908078
Presotto, E. M. et al. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. J. Endocrinol. Invest. 43, 337–345 (2020).
pubmed: 31542865
Prasad, V. & Kaestner, V. Nivolumab and pembrolizumab: monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Semin. Oncol. 44, 132–135 (2017).
pubmed: 28923211
Brahmer, J. R. et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 28, 3167–3175 (2010).
pubmed: 20516446
pmcid: 20516446
Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012).
pubmed: 22658127
pmcid: 3544539
Taube, J. M. et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin. Cancer Res. 20, 5064–5074 (2014).
pubmed: 24714771
pmcid: 4185001
Zou, W. & Chen, L. Inhibitory B7-family molecules in the tumour microenvironment. Nat. Rev. Immunol. 8, 467–477 (2008).
pubmed: 18500231
Fankhauser, C. D. et al. Comprehensive immunohistochemical analysis of PD-L1 shows scarce expression in castration-resistant prostate cancer. Oncotarget 9, 10284–10293 (2018).
pubmed: 29535806
Roth, T. J. et al. B7-H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. Cancer Res. 67, 7893–7900 (2007).
pubmed: 17686830
Zhang, J. et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 553, 91–95 (2018).
Mukhopadhyay, D. & Dasso, M. Modification in reverse: the SUMO proteases. Trends Biochem. Sci. 32, 286–295 (2007).
pubmed: 17499995
Yates, K. E., Korbel, G. A., Shtutman, M., Roninson, I. B. & DiMaio, D. Repression of the SUMO-specific protease Senp1 induces p53-dependent premature senescence in normal human fibroblasts. Aging Cell 7, 609–621 (2008).
pubmed: 18616636
pmcid: 2745089
Bischof, O. et al. The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis. Mol. Cell 22, 783–794 (2006).
pubmed: 16793547
Drag, M., Mikolajczyk, J., Krishnakumar, I. M., Huang, Z. & Salvesen, G. S. Activity profiling of human deSUMOylating enzymes (SENPs) with synthetic substrates suggests an unexpected specificity of two newly characterized members of the family. Biochem. J. 409, 461–469 (2008).
pubmed: 17916063
Itahana, Y., Yeh, E. T. & Zhang, Y. Nucleocytoplasmic shuttling modulates activity and ubiquitination-dependent turnover of SUMO-specific protease 2. Mol. Cell Biol. 26, 4675–4689 (2006).
pubmed: 16738331
pmcid: 1489137
Gong, L. & Yeh, E. T. Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3. J. Biol. Chem. 281, 15869–15877 (2006).
pubmed: 16608850
Bawa-Khalfe, T. et al. Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition. Proc. Natl Acad. Sci. USA 109, 17466–17471 (2012).
pubmed: 23045645
Lin, F. M. et al. SUMOylation of HP1α supports association with ncRNA to define responsiveness of breast cancer cells to chemotherapy. Oncotarget 7, 30336–30349 (2016).
pubmed: 27107417
pmcid: 5058684
Gonzalez-Prieto, R., Cuijpers, S. A., Kumar, R., Hendriks, I. A. & Vertegaal, A. C. c-Myc is targeted to the proteasome for degradation in a SUMOylation-dependent manner, regulated by PIAS1, SENP7 and RNF4. Cell Cycle 14, 1859–1872 (2015).
pubmed: 25895136
pmcid: 4613540
Zhu, H. et al. SPOP E3 ubiquitin ligase adaptor promotes cellular senescence by degrading the SENP7 deSUMOylase. Cell Rep. 13, 1183–1193 (2015).
pubmed: 26527005
pmcid: 4644472
Xu, J., Wu, R. C. & O’Malley, B. W. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat. Rev. Cancer 9, 615–630 (2009).
pubmed: 19701241
pmcid: 2908510
Zhou, X. E. et al. Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. J. Biol. Chem. 285, 9161–9171 (2010).
pubmed: 20086010
pmcid: 2838335
Heemers, H. V. et al. Differential regulation of steroid nuclear receptor coregulator expression between normal and neoplastic prostate epithelial cells. Prostate 70, 959–970 (2010).
pubmed: 20166126
pmcid: 2875314
Eedunuri, V. K. et al. miR-137 targets p160 steroid receptor coactivators SRC1, SRC2, and SRC3 and inhibits cell proliferation. Mol. Endocrinol. 29, 1170–1183 (2015).
pubmed: 26066330
pmcid: 4518002
Xiong, W. et al. Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through the SRC3/IGF1R/AKT pathway. Int. J. Biochem. Cell Biol. 94, 125–132 (2018).
pubmed: 29225160
Li, C. et al. Tumor-suppressor role for the SPOP ubiquitin ligase in signal-dependent proteolysis of the oncogenic co-activator SRC-3/AIB1. Oncogene 30, 4350–4364 (2011).
pubmed: 21577200
pmcid: 3158261
Kikuchi, M. et al. TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells. Biochim. Biophys. Acta 1793, 1828–1836 (2009).
pubmed: 19909775
Groner, A. C. et al. TRIM24 is an oncogenic transcriptional activator in prostate cancer. Cancer Cell 29, 846–858 (2016).
pubmed: 27238081
pmcid: 5124371
Zhu, K. et al. SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. Nucleic Acids Res. 45, 92–105 (2017).
pubmed: 27614073
Harb, O. A. et al. SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): clinicopathological and prognostic significance. Pathophysiology 25, 335–345 (2018).
pubmed: 29801752
Chauhan, A., Bhattacharyya, S., Ojha, R., Mandal, A. K. & Singh, S. K. Speckle-type POZ protein as a diagnostic biomarker in renal cell carcinoma. J. Cancer Res. Ther. 14, 977–982 (2018).
pubmed: 30197334
Nagy, A., Lanczky, A., Menyhart, O. & Gyorffy, B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci. Rep. 8, 9227 (2018).
pubmed: 29907753
pmcid: 6003936
Anaya, J. OncoLnc: linking TCGA survival data to mRNAs, miRNAs, and lncRNAs. PeerJ Computer Sci. 2, e67 (2016).
Zhao, W., Zhou, J., Deng, Z., Gao, Y. & Cheng, Y. SPOP promotes tumor progression via activation of β-catenin/TCF4 complex in clear cell renal cell carcinoma. Int. J. Oncol. 49, 1001–1008 (2016).
pubmed: 27572476
Puisieux, A., Brabletz, T. & Caramel, J. Oncogenic roles of EMT-inducing transcription factors. Nat. Cell Biol. 16, 488–494 (2014).
pubmed: 24875735
Tam, W. L. & Weinberg, R. A. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med. 19, 1438–1449 (2013).
pubmed: 24202396
pmcid: 4190672
Liu, X., Sun, G. & Sun, X. RNA interference-mediated silencing of speckle-type POZ protein promotes apoptosis of renal cell cancer cells. Onco Targets Ther. 9, 2393–2402 (2016).
pubmed: 27143934
pmcid: 4846068
He, D. et al. ASC-J9 suppresses renal cell carcinoma progression by targeting an androgen receptor-dependent HIF2α/VEGF signaling pathway. Cancer Res. 74, 4420–4430 (2014).
pubmed: 24924778
Adelaiye-Ogala, R. et al. Therapeutic targeting of sunitinib-induced AR phosphorylation in renal cell carcinoma. Cancer Res. 78, 2886–2896 (2018).
pubmed: 29572225
pmcid: 7001156
Chi, J. T. et al. Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers. PLoS Med. 3, e47 (2006).
pubmed: 16417408
pmcid: 1334226
Wagner, E. J. & Carpenter, P. B. Understanding the language of Lys36 methylation at histone H3. Nat. Rev. Mol. Cell Biol. 13, 115–126 (2012).
pubmed: 22266761
pmcid: 3969746
Venkatesh, S. et al. Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes. Nature 489, 452–455 (2012).
pubmed: 22914091
Larkin, J., Goh, X. Y., Vetter, M., Pickering, L. & Swanton, C. Epigenetic regulation in RCC: opportunities for therapeutic intervention? Nat. Rev. Urol. 9, 147–155 (2012).
pubmed: 22249190
Varela, I. et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469, 539–542 (2011).
pubmed: 21248752
pmcid: 3030920
Dalgliesh, G. L. et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463, 360–363 (2010).
pubmed: 20054297
pmcid: 2820242
Simon, J. M. et al. Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects. Genome Res. 24, 241–250 (2014).
pubmed: 24158655
pmcid: 3912414
Li, F. et al. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα. Cell 153, 590–600 (2013).
pubmed: 23622243
pmcid: 3641580
Pfister, S. X. et al. SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability. Cell Rep. 7, 2006–2018 (2014).
pubmed: 24931610
pmcid: 4074340
Carvalho, S. et al. SETD2 is required for DNA double-strand break repair and activation of the p53-mediated checkpoint. Elife 3, e02482 (2014).
pubmed: 24843002
pmcid: 4038841
Aymard, F. et al. Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat. Struct. Mol. Biol. 21, 366–374 (2014).
pubmed: 24658350
pmcid: 4300393
Errington, W. J. et al. Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase. Structure 20, 1141–1153 (2012).
pubmed: 22632832