Oncogene PRR14 promotes breast cancer through activation of PI3K signal pathway and inhibition of CHEK2 pathway.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
02
01
2020
accepted:
21
05
2020
revised:
20
05
2020
entrez:
17
6
2020
pubmed:
17
6
2020
medline:
13
4
2021
Statut:
epublish
Résumé
Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast cancer by inhibiting CHEK2's activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast cancer, which protects cells from apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast cancer.
Identifiants
pubmed: 32541902
doi: 10.1038/s41419-020-2640-8
pii: 10.1038/s41419-020-2640-8
pmc: PMC7296039
doi:
Substances chimiques
Chromosomal Proteins, Non-Histone
0
PRR14 protein, human
0
Checkpoint Kinase 2
EC 2.7.1.11
CHEK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
464Références
Zink, D., Fischer, A. H. & Nickerson, J. A. Nuclear structure in cancer cells. Nat. Rev. Cancer 4, 677–687 (2004).
pubmed: 15343274
doi: 10.1038/nrc1430
Gradishar, W. J. et al. Breast cancer version 2.2015. J. Natl Compr. Cancer Netw. 13, 448–475 (2015).
doi: 10.6004/jnccn.2015.0060
Elston, C. W. & Ellis, I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19, 403–410 (1991).
pubmed: 1757079
pmcid: 1757079
doi: 10.1111/j.1365-2559.1991.tb00229.x
Volpi, A. et al. Prognostic relevance of histological grade and its components in node-negative breast cancer patients. Mod. Pathol. 17, 1038–1044 (2004).
pubmed: 15154006
doi: 10.1038/modpathol.3800161
Beck, A. H. et al. Systematic analysis of breast cancer morphology uncovers stromal features associated with survival. Sci. Transl. Med. 3, 108ra113 (2011).
pubmed: 22072638
doi: 10.1126/scitranslmed.3002564
Burke, B. & Stewart, C. L. The nuclear lamins: flexibility in function. Nat. Rev. Mol. Cell Biol. 14, 13–24 (2013).
pubmed: 23212477
doi: 10.1038/nrm3488
Chow, K. H., Factor, R. E. & Ullman, K. S. The nuclear envelope environment and its cancer connections. Nat. Rev. Cancer 12, 196–209 (2012).
pubmed: 22337151
pmcid: 4338998
doi: 10.1038/nrc3219
de Las Heras, J. I., Batrakou, D. G. & Schirmer, E. C. Cancer biology and the nuclear envelope: a convoluted relationship. Semin Cancer Biol. 23, 125–137 (2013).
pubmed: 22311402
doi: 10.1016/j.semcancer.2012.01.008
Lammerding, J. et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest 113, 370–378 (2004).
pubmed: 14755334
pmcid: 324542
doi: 10.1172/JCI200419670
Ognibene, A. et al. Nuclear changes in a case of X-linked Emery-Dreifuss muscular dystrophy. Muscle Nerve 22, 864–869 (1999).
pubmed: 10398203
doi: 10.1002/(SICI)1097-4598(199907)22:7<864::AID-MUS8>3.0.CO;2-G
Chen, C. Y. et al. Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell 149, 565–577 (2012).
pubmed: 22541428
pmcid: 3340584
doi: 10.1016/j.cell.2012.01.059
Kayman-Kurekci, G. et al. Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene related to nuclear envelopathies. Neuromuscul. Disord. 24, 624–633 (2014).
pubmed: 24856141
doi: 10.1016/j.nmd.2014.04.007
Zhang, Q. et al. Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum. Mol. Genet. 16, 2816–2833 (2007).
pubmed: 17761684
doi: 10.1093/hmg/ddm238
Sakuma, S. & D’Angelo, M. A. The roles of the nuclear pore complex in cellular dysfunction, aging and disease. Semin. Cell Dev. Biol. 68, 72–84 (2017).
pubmed: 28506892
pmcid: 5568450
doi: 10.1016/j.semcdb.2017.05.006
Aljada, A. et al. Altered Lamin A/C splice variant expression as a possible diagnostic marker in breast cancer. Cell Oncol. 39, 161–174 (2016).
doi: 10.1007/s13402-015-0265-1
Willis, N. D. et al. Lamin A/C is a risk biomarker in colorectal cancer. PLoS ONE 3, e2988 (2008).
pubmed: 18714339
pmcid: 2496895
doi: 10.1371/journal.pone.0002988
Sun, S., Xu, M. Z., Poon, R. T., Day, P. J. & Luk, J. M. Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients. J. Proteome Res. 9, 70–78 (2010).
pubmed: 19522540
doi: 10.1021/pr9002118
Poleshko, A. et al. The human protein PRR14 tethers heterochromatin to the nuclear lamina during interphase and mitotic exit. Cell Rep. 5, 292–301 (2013).
pubmed: 24209742
doi: 10.1016/j.celrep.2013.09.024
Yang, M. & Yuan, Z. M. A novel role of PRR14 in the regulation of skeletal myogenesis. Cell Death Dis. 6, e1734 (2015).
pubmed: 25906157
pmcid: 4650536
doi: 10.1038/cddis.2015.103
Xiao, S. & Yang, M. Discovery of a novel target for cancer: PRR14. Cell Death Dis. 7, e2502 (2016).
pubmed: 27906191
pmcid: 5261014
doi: 10.1038/cddis.2016.401
Yang, M., Lewinska, M., Fan, X., Zhu, J. & Yuan, Z. M. PRR14 is a novel activator of the PI3K pathway promoting lung carcinogenesis. Oncogene 35, 5527–5538 (2016).
pubmed: 27041574
pmcid: 5787860
doi: 10.1038/onc.2016.93
Petsalaki, E. & Zachos, G. Chk2 prevents mitotic exit when the majority of kinetochores are unattached. J. Cell Biol. 205, 339–356 (2014).
pubmed: 24798733
pmcid: 4018780
doi: 10.1083/jcb.201310071
Ahn, J. Y., Schwarz, J. K., Piwnica-Worms, H. & Canman, C. E. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res. 60, 5934–5936 (2000).
pubmed: 11085506
Matsuoka, S. et al. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc. Natl Acad. Sci. USA 97, 10389–10394 (2000).
pubmed: 10973490
doi: 10.1073/pnas.190030497
Shieh, S. Y., Taya, Y. & Prives, C. DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization. EMBO J. 18, 1815–1823 (1999).
pubmed: 10202145
pmcid: 1171267
doi: 10.1093/emboj/18.7.1815
Lee, J. S., Collins, K. M., Brown, A. L., Lee, C. H. & Chung, J. H. hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404, 201–204 (2000).
pubmed: 10724175
doi: 10.1038/35004614
Bahassi, E. M. et al. The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage. Oncogene 27, 3977–3985 (2008).
pubmed: 18317453
doi: 10.1038/onc.2008.17
Yang, S., Kuo, C., Bisi, J. E. & Kim, M. K. PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2. Nat. Cell Biol. 4, 865–870 (2002).
pubmed: 12402044
doi: 10.1038/ncb869
Stevens, C., Smith, L. & La Thangue, N. B. Chk2 activates E2F-1 in response to DNA damage. Nat. Cell Biol. 5, 401–409 (2003).
pubmed: 12717439
doi: 10.1038/ncb974
Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J. & Lukas, J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410, 842–847 (2001).
pubmed: 11298456
doi: 10.1038/35071124
Ahn, J. & Prives, C. Checkpoint kinase 2 (Chk2) monomers or dimers phosphorylate Cdc25C after DNA damage regardless of threonine 68 phosphorylation. J. Biol. Chem. 277, 48418–48426 (2002).
pubmed: 12386164
doi: 10.1074/jbc.M208321200
Bailey, M. H. et al. Comprehensive characterization of cancer driver genes and mutations. Cell 173, 371–385 e318 (2018).
pubmed: 29625053
pmcid: 6029450
doi: 10.1016/j.cell.2018.02.060
Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012).
doi: 10.1038/nature11412
Pinkel, D. et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat. Genet. 20, 207–211 (1998).
pubmed: 9771718
doi: 10.1038/2524
Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).
pubmed: 10963602
doi: 10.1038/35021093
pmcid: 10963602
Sorlie, T. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98, 10869–10874 (2001).
pubmed: 11553815
doi: 10.1073/pnas.191367098
Parker, J. S. et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J. Clin. Oncol. 27, 1160–1167 (2009).
pubmed: 2667820
pmcid: 2667820
doi: 10.1200/JCO.2008.18.1370
Shaw, R. J. & Cantley, L. C. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441, 424–430 (2006).
pubmed: 16724053
doi: 10.1038/nature04869
Engelman, J. A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550–562 (2009).
pubmed: 19629070
doi: 10.1038/nrc2664
Fischer, M., Quaas, M., Steiner, L. & Engeland, K. The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes. Nucleic Acids Res. 44, 164–174 (2016).
pubmed: 26384566
doi: 10.1093/nar/gkv927
Reinhardt, H. C., Aslanian, A. S., Lees, J. A. & Yaffe, M. B. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 11, 175–189 (2007).
pubmed: 17292828
pmcid: 2742175
doi: 10.1016/j.ccr.2006.11.024
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J. & Howley, P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129–1136 (1990).
pubmed: 2175676
doi: 10.1016/0092-8674(90)90409-8
Martinez-Zapien, D. et al. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature 529, 541–545 (2016).
pubmed: 26789255
pmcid: 4853763
doi: 10.1038/nature16481
Casamayor, A., Morrice, N. A. & Alessi, D. R. Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem J. 342, 287–292 (1999).
pubmed: 10455013
pmcid: 1220463
doi: 10.1042/bj3420287
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A. & Chen, D. J. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem. 276, 42462–42467 (2001).
pubmed: 11571274
doi: 10.1074/jbc.C100466200
Arienti, K. L. et al. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J. Med. Chem. 48, 1873–1885 (2005).
pubmed: 15771432
doi: 10.1021/jm0495935
Perez-Llamas, C. & Lopez-Bigas, N. Gitools: analysis and visualisation of genomic data using interactive heat-maps. PLoS ONE 6, e19541 (2011).
pubmed: 21602921
pmcid: 3094337
doi: 10.1371/journal.pone.0019541
Kamburov, A., Stelzl, U., Lehrach, H. & Herwig, R. The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Res. 41, D793–D800 (2013).
pubmed: 23143270
doi: 10.1093/nar/gks1055
Ricoult, S. J., Yecies, J. L., Ben-Sahra, I. & Manning, B. D. Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene 35, 1250–1260 (2016).
pubmed: 26028026
doi: 10.1038/onc.2015.179