P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
05
12
2020
accepted:
20
08
2021
revised:
09
08
2021
pubmed:
3
9
2021
medline:
27
1
2022
entrez:
2
9
2021
Statut:
ppublish
Résumé
Yes-associated protein 1 (YAP1), a key player in the Hippo pathway, has been shown to play a critical role in tumor progression. However, the role of YAP1 in prostate cancer cell invasion, migration, and metastasis is not well defined. Through functional, transcriptomic, epigenomic, and proteomic analyses, we showed that prolyl hydroxylation of YAP1 plays a critical role in the suppression of cell migration, invasion, and metastasis in prostate cancer. Knockdown (KD) or knockout (KO) of YAP1 led to an increase in cell migration, invasion, and metastasis in prostate cancer cells. Microarray analysis showed that the EMT pathway was activated in Yap1-KD cells. ChIP-seq analysis showed that YAP1 target genes are enriched in pathways regulating cell migration. Mass spectrometry analysis identified P4H prolyl hydroxylase in the YAP1 complex and YAP1 was hydroxylated at multiple proline residues. Proline-to-alanine mutations of YAP1 isoform 3 identified proline 174 as a critical residue, and its hydroxylation suppressed cell migration, invasion, and metastasis. KO of P4ha2 led to an increase in cell migration and invasion, which was reversed upon Yap1 KD. Our study identified a novel regulatory mechanism of YAP1 by which P4HA2-dependent prolyl hydroxylation of YAP1 determines its transcriptional activities and its function in prostate cancer metastasis.
Identifiants
pubmed: 34471235
doi: 10.1038/s41388-021-02000-3
pii: 10.1038/s41388-021-02000-3
pmc: PMC8526415
mid: NIHMS1739227
doi:
Substances chimiques
YAP-Signaling Proteins
0
Yap1 protein, mouse
0
P4HA2 protein, human
EC 1.14.11.-
Prolyl Hydroxylases
EC 1.14.11.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6049-6056Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA140388
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA194289
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA174798
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Calses PC, Crawford JJ, Lill JR, Dey A. Hippo pathway in cancer: aberrant regulation and therapeutic opportunities. Trends Cancer. 2019;5:297–307.
pubmed: 31174842
doi: 10.1016/j.trecan.2019.04.001
Ehsanian R, Brown M, Lu H, Yang XP, Pattatheyil A, Yan B, et al. YAP dysregulation by phosphorylation or DeltaNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer subsets. Oncogene. 2010;29:6160–71.
pubmed: 20729916
pmcid: 2991596
doi: 10.1038/onc.2010.339
Yuan M, Tomlinson V, Lara R, Holliday D, Chelala C, Harada T, et al. Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death Differ. 2008;15:1752–9.
pubmed: 18617895
doi: 10.1038/cdd.2008.108
Yu SJ, Hu JY, Kuang XY, Luo JM, Hou YF, Di GH, et al. MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clin Cancer Res. 2013;19:1389–99.
pubmed: 23340296
doi: 10.1158/1078-0432.CCR-12-1959
Matallanas D, Romano D, Yee K, Meissl K, Kucerova L, Piazzolla D, et al. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell. 2007;27:962–75.
pubmed: 17889669
pmcid: 2821687
doi: 10.1016/j.molcel.2007.08.008
Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, et al. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med. 2014;20:599–606.
pubmed: 24813251
pmcid: 4057660
doi: 10.1038/nm.3562
Levy D, Adamovich Y, Reuven N, Shaul Y. The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ. 2007;14:743–51.
pubmed: 17110958
doi: 10.1038/sj.cdd.4402063
Cheung P, Xiol J, Dill MT, Yuan WC, Panero R, Roper J, et al. Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer. Cell Stem Cell. 2020;27:590–604.e9.
pubmed: 32730753
doi: 10.1016/j.stem.2020.07.003
Ou C, Sun Z, Li S, Li G, Li X, Ma J. Dual roles of yes-associated protein (YAP) in colorectal cancer. Oncotarget. 2017;8:75727–41.
pubmed: 29088905
pmcid: 5650460
doi: 10.18632/oncotarget.20155
Cheng S, Prieto-Dominguez N, Yang S, Connelly ZM, StPierre S, Rushing B, et al. The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer. Prostate Cancer Prostatic Dis. 2020;23:661–9.
pubmed: 32313141
pmcid: 7572469
doi: 10.1038/s41391-020-0229-z
Nguyen LT, Tretiakova MS, Silvis MR, Lucas J, Klezovitch O, Coleman I, et al. ERG activates the YAP1 transcriptional program and induces the development of age-related prostate tumors. Cancer Cell. 2015;27:797–808.
pubmed: 26058078
pmcid: 4461839
doi: 10.1016/j.ccell.2015.05.005
Wang G, Lu X, Dey P, Deng P, Wu CC, Jiang S, et al. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov. 2016;6:80–95.
pubmed: 26701088
doi: 10.1158/2159-8290.CD-15-0224
Zhang L, Yang S, Chen X, Stauffer S, Yu F, Lele SM, et al. The Hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of prostate cancer cells. Mol Cell Biol. 2015;35:1350–62.
pubmed: 25645929
pmcid: 4372700
doi: 10.1128/MCB.00102-15
Kuser-Abali G, Alptekin A, Lewis M, Garraway IP, Cinar B. YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer. Nat Commun. 2015;6:8126.
pubmed: 28230103
doi: 10.1038/ncomms9126
Chen YA, Lu CY, Cheng TY, Pan SH, Chen HF, Chang NS. WW domain-containing proteins YAP and TAZ in the Hippo pathway as key regulators in stemness maintenance, tissue homeostasis, and tumorigenesis. Front Oncol. 2019;9:60.
pubmed: 30805310
pmcid: 6378284
doi: 10.3389/fonc.2019.00060
Yan F, Qian M, He Q, Zhu H, Yang B. The posttranslational modifications of Hippo-YAP pathway in cancer. Biochim Biophys Acta Gen Subj. 2020;1864:129397.
pubmed: 31306710
doi: 10.1016/j.bbagen.2019.07.006
Zurlo G, Guo J, Takada M, Wei W, Zhang Q. New insights into protein hydroxylation and its important role in human diseases. Biochim Biophys Acta. 2016;1866:208–20.
pubmed: 27663420
pmcid: 5138100
Gorres KL, Raines RT. Prolyl 4-hydroxylase. Crit Rev Biochem Mol Biol. 2010;45:106–24.
pubmed: 20199358
pmcid: 2841224
doi: 10.3109/10409231003627991
Su W, Han HH, Wang Y, Zhang B, Zhou B, Cheng Y, et al. The polycomb repressor complex 1 drives double-negative prostate cancer metastasis by coordinating stemness and immune suppression. Cancer Cell. 2019;36:139–55.e10.
pubmed: 31327655
pmcid: 7210785
doi: 10.1016/j.ccell.2019.06.009
Kapoor A, Yao W, Ying H, Hua S, Liewen A, Wang Q, et al. Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. Cell. 2014;158:185–97.
pubmed: 24954535
pmcid: 4109295
doi: 10.1016/j.cell.2014.06.003
Shao DD, Xue W, Krall EB, Bhutkar A, Piccioni F, Wang X, et al. KRAS and YAP1 converge to regulate EMT and tumor survival. Cell. 2014;158:171–84.
pubmed: 24954536
pmcid: 4110062
doi: 10.1016/j.cell.2014.06.004
Hiemer SE, Szymaniak AD, Varelas X. The transcriptional regulators TAZ and YAP direct transforming growth factor beta-induced tumorigenic phenotypes in breast cancer cells. J Biol Chem. 2014;289:13461–74.
pubmed: 24648515
pmcid: 4036353
doi: 10.1074/jbc.M113.529115
Kim T, Yang SJ, Hwang D, Song J, Kim M, Kyum Kim S, et al. A basal-like breast cancer-specific role for SRF-IL6 in YAP-induced cancer stemness. Nat Commun. 2015;6:10186.
pubmed: 26671411
doi: 10.1038/ncomms10186
Isfort I, Cyra M, Elges S, Kailayangiri S, Altvater B, Rossig C, et al. SS18-SSX-dependent YAP/TAZ signaling in synovial sarcoma. Clin Cancer Res. 2019;25:3718–31.
pubmed: 30814111
doi: 10.1158/1078-0432.CCR-17-3553
Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012;149:656–70.
pubmed: 22541435
pmcid: 3472002
doi: 10.1016/j.cell.2012.01.058
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.
pubmed: 16199517
pmcid: 1239896
doi: 10.1073/pnas.0506580102
Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol. 2015;17:1218–27.
pubmed: 26258633
pmcid: 6186417
doi: 10.1038/ncb3216
Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–89.
pubmed: 20513432
pmcid: 2898526
doi: 10.1016/j.molcel.2010.05.004
Li S, Wan C, Zheng R, Fan J, Dong X, Meyer CA, et al. Cistrome-GO: a web server for functional enrichment analysis of transcription factor ChIP-seq peaks. Nucleic Acids Res. 2019;47:W206–W211.
pubmed: 31053864
pmcid: 6602521
doi: 10.1093/nar/gkz332
Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21:2747–61.
pubmed: 17974916
pmcid: 2045129
doi: 10.1101/gad.1602907
Becker JS, Nicetto D, Zaret KS. H3K9me3-dependent heterochromatin: barrier to cell fate changes. Trends Genet. 2016;32:29–41.
pubmed: 26675384
doi: 10.1016/j.tig.2015.11.001
Pekowska A, Benoukraf T, Zacarias-Cabeza J, Belhocine M, Koch F, Holota H, et al. H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J. 2011;30:4198–210.
pubmed: 21847099
pmcid: 3199384
doi: 10.1038/emboj.2011.295
Zhang B, Chambers KJ, Faller DV, Wang S. Reprogramming of the SWI/SNF complex for co-activation or co-repression in prohibitin-mediated estrogen receptor regulation. Oncogene. 2007;26:7153–7.
pubmed: 17486062
doi: 10.1038/sj.onc.1210509
Nagl NG Jr., Wang X, Patsialou A, Van Scoy M, Moran E. Distinct mammalian SWI/SNF chromatin remodeling complexes with opposing roles in cell-cycle control. EMBO J. 2007;26:752–63.
pubmed: 17255939
pmcid: 1794396
doi: 10.1038/sj.emboj.7601541
Underhill C, Qutob MS, Yee SP, Torchia J. A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor KAP-1. J Biol Chem. 2000;275:40463–70.
pubmed: 11013263
doi: 10.1074/jbc.M007864200
Hoxha S, Shepard A, Troutman S, Diao H, Doherty JR, Janiszewska M, et al. YAP-mediated recruitment of YY1 and EZH2 represses transcription of key cell-cycle regulators. Cancer Res. 2020;80:2512–22.
pubmed: 32409309
pmcid: 7299785
doi: 10.1158/0008-5472.CAN-19-2415
Kim M, Kim T, Johnson RL, Lim DS. Transcriptional co-repressor function of the Hippo pathway transducers YAP and TAZ. Cell Rep. 2015;11:270–82.
pubmed: 25843714
doi: 10.1016/j.celrep.2015.03.015
Zhao B, Kim J, Ye X, Lai ZC, Guan KL. Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein. Cancer Res. 2009;69:1089–98.
pubmed: 19141641
doi: 10.1158/0008-5472.CAN-08-2997
Ma S, Meng Z, Chen R, Guan KL. The Hippo pathway: biology and pathophysiology. Annu Rev Biochem. 2019;88:577–604.
pubmed: 30566373
doi: 10.1146/annurev-biochem-013118-111829
Chakravarthi BV, Pathi SS, Goswami MT, Cieslik M, Zheng H, Nallasivam S, et al. The miR-124-prolyl hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression. Oncotarget. 2014;5:6654–69.
pubmed: 25115393
pmcid: 4196154
doi: 10.18632/oncotarget.2208
van Huizen NA, Burgers PC, Saintmont F, Brocorens P, Gerbaux P, Stingl C, et al. Identification of 4-hydroxyproline at the Xaa position in collagen by mass spectrometry. J Proteome Res. 2019;18:2045–51.
pubmed: 30945869
doi: 10.1021/acs.jproteome.8b00930
Discher DE, Smith L, Cho S, Colasurdo M, Garcia AJ, Safran S. Matrix mechanosensing: from scaling concepts in ‘omics data to mechanisms in the nucleus, regeneration, and cancer. Annu Rev Biophys. 2017;46:295–315.
pubmed: 28532215
pmcid: 5444306
doi: 10.1146/annurev-biophys-062215-011206
Ozdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu CC, Simpson TR, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25:719–34.
pubmed: 24856586
pmcid: 4180632
doi: 10.1016/j.ccr.2014.04.005
Holster T, Pakkanen O, Soininen R, Sormunen R, Nokelainen M, Kivirikko KI, et al. Loss of assembly of the main basement membrane collagen, type IV, but not fibril-forming collagens and embryonic death in collagen prolyl 4-hydroxylase I null mice. J Biol Chem. 2007;282:2512–9.
pubmed: 17135260
doi: 10.1074/jbc.M606608200
Aro E, Salo AM, Khatri R, Finnila M, Miinalainen I, Sormunen R, et al. Severe extracellular matrix abnormalities and chondrodysplasia in mice lacking collagen prolyl 4-hydroxylase isoenzyme II in combination with a reduced amount of isoenzyme I. J Biol Chem. 2015;290:16964–78.
pubmed: 26001784
pmcid: 4505441
doi: 10.1074/jbc.M115.662635
Xiong G, Deng L, Zhu J, Rychahou PG, Xu R. Prolyl-4-hydroxylase alpha subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer. 2014;14:1.
pubmed: 24383403
pmcid: 3880410
doi: 10.1186/1471-2407-14-1
Gilkes DM, Chaturvedi P, Bajpai S, Wong CC, Wei H, Pitcairn S, et al. Collagen prolyl hydroxylases are essential for breast cancer metastasis. Cancer Res. 2013;73:3285–96.
pubmed: 23539444
pmcid: 3674184
doi: 10.1158/0008-5472.CAN-12-3963