Functional significance of Aurora kinases-p53 protein family interactions in cancer

Frontiers in Oncology

Volumn 6, Issue NOV, 2016, Pages

  Sasai, Kaori ^a   Treekitkarnmongkol, Warapen ^b   Kai, Kazuharu ^b   Katayama, Hiroshi ^a   Sen, Subrata ^b  

^a OKAYAMA UNIVERSITY   (Japan)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Aurora kinases; Centrosome amplification; Chromosome instability; P53 tumor suppressor protein family; Pluripotency; Tumorigenesis

Indexed keywords

AURORA A KINASE; AURORA B KINASE; AURORA C KINASE; AURORA KINASE; CELL CYCLE PROTEIN 20; CYCLIN D; CYCLIN DEPENDENT KINASE; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; MESSENGER RNA; NUCLEOPHOSMIN; PROTEIN MDM2; PROTEIN P53; PROTEIN P73; STAT3 PROTEIN;

CENTROSOME; DOWN REGULATION; EMBRYONIC STEM CELL; FUNCTIONAL GENOMICS; GENE EXPRESSION; GENETIC ENGINEERING; HUMAN; M PHASE CELL CYCLE CHECKPOINT; MOUSE MODEL; NEOPLASM; NEUROBLASTOMA; NONHUMAN; PLURIPOTENT STEM CELL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; REVIEW; SIGNAL TRANSDUCTION; STEM CELL SELF-RENEWAL; TRANSGENIC MOUSE;

EID: 85006515740     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2016.00247     Document Type: Review

References (96)

1. Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF. Abnormal centrosome amplification in the absence of p53. Science (1996) 271(5256):1744-7. doi:10.1126/science.271.5256.1744
2. Bischoff FZ, Yim SO, Pathak S, Grant G, Siciliano MJ, Giovanella BC, et al. Spontaneous abnormalities in normal fibroblasts from patients with Li-Fraumeni cancer syndrome: aneuploidy and immortalization. Cancer Res (1990) 50(24):7979-84.
3. Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet (1998) 20(2):189-93. doi:10.1038/2496
4. Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, et al. A homologue of Drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J (1998) 17(11):3052-65. doi:10.1093/emboj/17.11.3052
5. Marumoto T, Hirota T, Morisaki T, Kunitoku N, Zhang D, Ichikawa Y, et al. Roles of Aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells. Genes Cells (2002) 7(11):1173-82. doi:10.1046/j.1365-2443.2002.00592.x
6. Chen SS, Chang PC, Cheng YW, Tang FM, Lin YS. Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function. EMBO J (2002) 21(17):4491-9. doi:10.1093/emboj/cdf409
7. Eyers PA, Maller JL. Regulation of Xenopus Aurora A activation by TPX2. J Biol Chem (2004) 279(10):9008-15. doi:10.1074/jbc.M312424200
8. Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, et al. Phosphorylation by Aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet (2004) 36(1):55-62. doi:10.1038/ng1279
9. Liu Q, Kaneko S, Yang L, Feldman RI, Nicosia SV, Chen J, et al. Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem (2004) 279(50):52175-82. doi:10.1074/jbc.M406802200
10. Hsueh KW, Fu SL, Chang CB, Chang YL, Lin CH. A novel Aurora-A-mediated phosphorylation of p53 inhibits its interaction with MDM2. Biochim Biophys Acta (2013) 1834(2):508-15. doi:10.1016/j.bbapap.2012.11.005
11. Warnock LJ, Raines SA, Milner J. Aurora A mediates cross-talk between N-and C-terminal post-translational modifications of p53. Cancer Biol Ther (2011) 12(12):1059-68. doi:10.4161/cbt.12.12.18141
12. Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, et al. Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J (1999) 18(23):6845-54. doi:10.1093/emboj/18.23.6845
13. Moumen A, Masterson P, O'Connor MJ, Jackson SP. hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Cell (2005) 123(6):1065-78. doi:10.1016/j.cell.2005.09.032
14. Enge M, Bao W, Hedstrom E, Jackson SP, Moumen A, Selivanova G. MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53. Cancer Cell (2009) 15(3):171-83. doi:10.1016/j.ccr.2009.01.019
15. Hsueh KW, Fu SL, Huang CY, Lin CH. Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53. FEBS Lett (2011) 585(17):2671-5. doi:10.1016/j.febslet.2011.07.031
16. Dar AA, Zaika A, Piazuelo MB, Correa P, Koyama T, Belkhiri A, et al. Frequent overexpression of Aurora kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer (2008) 112(8):1688-98. doi:10.1002/cncr.23371
17. Sehdev V, Katsha A, Arras J, Peng D, Soutto M, Ecsedy J, et al. HDM2 regulation by AURKA promotes cell survival in gastric cancer. Clin Cancer Res (2014) 20(1):76-86. doi:10.1158/1078-0432.CCR-13-1187
18. Wu L, Ma CA, Zhao Y, Jain A. Aurora B interacts with NIR-p53, leading to p53 phosphorylation in its DNA-binding domain and subsequent functional suppression. J Biol Chem (2011) 286(3):2236-44. doi:10.1074/jbc.M110.174755
19. Gully CP, Velazquez-Torres G, Shin JH, Fuentes-Mattei E, Wang E, Carlock C, et al. Aurora B kinase phosphorylates and instigates degradation of p53. Proc Natl Acad Sci U S A (2012) 109(24):E1513-22. doi:10.1073/pnas.1110287109
20. Huang YF, Chang MD, Shieh SY. TTK/hMps1 mediates the p53-dependent postmitotic checkpoint by phosphorylating p53 at Thr18. Mol Cell Biol (2009) 29(11):2935-44. doi:10.1128/MCB.01837-08
21. Ha GH, Baek KH, Kim HS, Jeong SJ, Kim CM, McKeon F, et al. p53 activation in response to mitotic spindle damage requires signaling via BubR1-mediated phosphorylation. Cancer Res (2007) 67(15):7155-64. doi:10.1158/0008-5472.CAN-06-3392
22. Wang YC, Tsai YS, Huang JL, Lee KW, Kuo CC, Wang CS, et al. Arecoline arrests cells at prometaphase by deregulating mitotic spindle assembly and spindle assembly checkpoint: implication for carcinogenesis. Oral Oncol (2010) 46(4):255-62. doi:10.1016/j.oraloncology.2010.01.003
23. Ha GH, Breuer EK. Mitotic kinases and p53 signaling. Biochem Res Int (2012) 2012:195903. doi:10.1155/2012/195903
24. Katayama H, Wang J, Treekitkarnmongkol W, Kawai H, Sasai K, Zhang H, et al. Aurora kinase-A inactivates DNA damage-induced apoptosis and spindle assembly checkpoint response functions of p73. Cancer Cell (2012) 21(2):196-211. doi:10.1016/j.ccr.2011.12.025
25. Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung CC, et al. TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev (2008) 22(19):2677-91. doi:10.1101/gad.1695308
26. Tomasini R, Tsuchihara K, Tsuda C, Lau SK, Wilhelm M, Ruffini A, et al. TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity. Proc Natl Acad Sci U S A (2009) 106(3):797-802. doi:10.1073/pnas.0812096106
27. Vernole P, Neale MH, Barcaroli D, Munarriz E, Knight RA, Tomasini R, et al. TAp73alpha binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. Cell Cycle (2009) 8(3):421-9. doi:10.4161/cc.8.3.7623
28. Nikulenkov F, Spinnler C, Li H, Tonelli C, Shi Y, Turunen M, et al. Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis. Cell Death Differ (2012) 19(12):1992-2002. doi:10.1038/cdd.2012.89
29. Katsha A, Arras J, Soutto M, Belkhiri A, El-Rifai W. AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers. Mol Oncol (2014) 8(8):1419-28. doi:10.1016/j.molonc.2014.05.012
30. He L, Yang H, Ma Y, Pledger WJ, Cress WD, Cheng JQ. Identification of Aurora-A as a direct target of E2F3 during G2/M cell cycle progression. J Biol Chem (2008) 283(45):31012-20. doi:10.1074/jbc.M803547200
31. Shao S, Wang Y, Jin S, Song Y, Wang X, Fan W, et al. Gadd45a interacts with Aurora-A and inhibits its kinase activity. J Biol Chem (2006) 281(39):28943-50. doi:10.1074/jbc.M600235200
32. Mao JH, Perez-Losada J, Wu D, Delrosario R, Tsunematsu R, Nakayama KI, et al. Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature (2004) 432(7018):775-9. doi:10.1038/nature03155
33. Wu CC, Yang TY, Yu CT, Phan L, Ivan C, Sood AK, et al. p53 negatively regulates Aurora A via both transcriptional and posttranslational regulation. Cell Cycle (2012) 11(18):3433-42. doi:10.4161/cc.21732
34. Teng CL, Hsieh YC, Phan L, Shin J, Gully C, Velazquez-Torres G, et al. FBXW7 is involved in Aurora B degradation. Cell Cycle (2012) 11(21):4059-68. doi:10.4161/cc.22381
35. Kwon YW, Kim IJ, Wu D, Lu J, Stock WA Jr, Liu Y, et al. Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development. Mol Cancer Res (2012) 10(6):834-44. doi:10.1158/1541-7786.MCR-12-0025
36. Mao JH, Wu D, Perez-Losada J, Jiang T, Li Q, Neve RM, et al. Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Cancer Cell (2007) 11(2):161-73. doi:10.1016/j.ccr.2006.11.025
37. Otto T, Horn S, Brockmann M, Eilers U, Schuttrumpf L, Popov N, et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell (2009) 15(1):67-78. doi:10.1016/j.ccr.2008.12.005
38. Brockmann M, Poon E, Berry T, Carstensen A, Deubzer HE, Rycak L, et al. Small molecule inhibitors of Aurora-A induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell (2013) 24(1):75-89. doi:10.1016/j.ccr.2013.05.005
39. Morozova O, Vojvodic M, Grinshtein N, Hansford LM, Blakely KM, Maslova A, et al. System-level analysis of neuroblastoma tumor-initiating cells implicates AURKB as a novel drug target for neuroblastoma. Clin Cancer Res (2010) 16(18):4572-82. doi:10.1158/1078-0432.CCR-10-0627
40. Bogen D, Wei JS, Azorsa DO, Ormanoglu P, Buehler E, Guha R, et al. Aurora B kinase is a potent and selective target in MYCN-driven neuroblastoma. Oncotarget (2015) 6(34):35247-62. doi:10.18632/oncotarget.6208
41. den Hollander J, Rimpi S, Doherty JR, Rudelius M, Buck A, Hoellein A, et al. Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood (2010) 116(9):1498-505. doi:10.1182/blood-2009-11-251074
42. Chou CH, Yang NK, Liu TY, Tai SK, Hsu DS, Chen YW, et al. Chromosome instability modulated by BMI1-AURKA signaling drives progression in head and neck cancer. Cancer Res (2013) 73(2):953-66. doi:10.1158/0008-5472.CAN-12-2397
43. Li Z, Sun Y, Chen X, Squires J, Nowroozizadeh B, Liang C, et al. p53 mutation directs AURKA overexpression via miR-25 and FBXW7 in prostatic small cell neuroendocrine carcinoma. Mol Cancer Res (2015) 13(3):584-91. doi:10.1158/1541-7786.MCR-14-0277-T
44. Schnepp RW, Khurana P, Attiyeh EF, Raman P, Chodosh SE, Oldridge DA, et al. A LIN28B-RAN-AURKA signaling network promotes neuroblastoma tumorigenesis. Cancer Cell (2015) 28(5):599-609. doi:10.1016/j.ccell.2015.09.012
45. Suh SS, Yoo JY, Nuovo GJ, Jeon YJ, Kim S, Lee TJ, et al. MicroRNAs/TP53 feedback circuitry in glioblastoma multiforme. Proc Natl Acad Sci U S A (2012) 109(14):5316-21. doi:10.1073/pnas.1202465109
46. Zheng F, Yue C, Li G, He B, Cheng W, Wang X, et al. Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype. Nat Commun (2016) 7:10180. doi:10.1038/ncomms10180
47. Slack A, Chen Z, Tonelli R, Pule M, Hunt L, Pession A, et al. The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma. Proc Natl Acad Sci U S A (2005) 102(3):731-6. doi:10.1073/pnas.0405495102
48. Slack AD, Chen Z, Ludwig AD, Hicks J, Shohet JM. MYCN-directed centrosome amplification requires MDM2-mediated suppression of p53 activity in neuroblastoma cells. Cancer Res (2007) 67(6):2448-55. doi:10.1158/0008-5472.CAN-06-1661
49. Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, et al. Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell (2000) 103(1):127-40. doi:10.1016/S0092-8674(00)00093-3
50. Bahtz R, Seidler J, Arnold M, Haselmann-Weiss U, Antony C, Lehmann WD, et al. GCP6 is a substrate of Plk4 and required for centriole duplication. J Cell Sci (2012) 125(Pt 2):486-96. doi:10.1242/jcs.093930
51. Nakamura T, Saito H, Takekawa M. SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress. Nat Commun (2013) 4:1775. doi:10.1038/ncomms2752
52. Fischer M, Quaas M, Wintsche A, Müller GA, Engeland K. Polo-like kinase 4 transcription is activated via CRE and NRF1 elements, repressed by DREAM through CDE/CHR sites and deregulated by HPV E7 protein. Nucleic Acids Res (2014) 42(1):163-80. doi:10.1093/nar/gkt849
53. Mikule K, Delaval B, Kaldis P, Jurcyzk A, Hergert P, Doxsey S. Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest. Nat Cell Biol (2007) 9(2):160-70. doi:10.1038/ncb1529
54. Song L, Dai T, Xiong H, Lin C, Lin H, Shi T, et al. Inhibition of centriole duplication by centrobin depletion leads to p38-p53 mediated cell-cycle arrest. Cell Signal (2010) 22(5):857-64. doi:10.1016/j.cellsig.2010.01.009
55. Suhail TV, Singh P, Manna TK. Suppression of centrosome protein TACC3 induces G1 arrest and cell death through activation of p38-p53-p21 stress signaling pathway. Eur J Cell Biol (2015) 94(2):90-100. doi:10.1016/j.ejcb.2014.12.001
56. Ma Z, Izumi H, Kanai M, Kabuyama Y, Ahn NG, Fukasawa K. Mortalin controls centrosome duplication via modulating centrosomal localization of p53. Oncogene (2006) 25(39):5377-90. doi:10.1038/sj.onc.1209543
57. Kanai M, Ma Z, Izumi H, Kim SH, Mattison CP, Winey M, et al. Physical and functional interaction between mortalin and Mps1 kinase. Genes Cells (2007) 12(6):797-810. doi:10.1111/j.1365-2443.2007.01091.x
58. Xu ZX, Zou WX, Lin P, Chang KS. A role for PML3 in centrosome duplication and genome stability. Mol Cell (2005) 17(5):721-32. doi:10.1016/j.molcel.2005.02.014
59. Reboutier D, Troadec MB, Cremet JY, Fukasawa K, Prigent C. Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89. J Cell Biol (2012) 197(1):19-26. doi:10.1083/jcb.201107134
60. Yang X, Li H, Zhou Z, Wang WH, Deng A, Andrisani O, et al. Plk1-mediated phosphorylation of Topors regulates p53 stability. J Biol Chem (2009) 284(28):18588-92. doi:10.1074/jbc.C109.001560
61. Lukasiewicz KB, Greenwood TM, Negron VC, Bruzek AK, Salisbury JL, Lingle WL. Control of centrin stability by Aurora A. PLoS One (2011) 6(6):e21291. doi:10.1371/journal.pone.0021291
62. Yang CH, Kasbek C, Majumder S, Yusof AM, Fisk HA. Mps1 phosphorylation sites regulate the function of centrin 2 in centriole assembly. Mol Biol Cell (2010) 21(24):4361-72. doi:10.1091/mbc.E10-04-0298
63. Boutros R, Mondesert O, Lorenzo C, Astuti P, McArthur G, Chircop M, et al. CDC25B overexpression stabilises centrin 2 and promotes the formation of excess centriolar foci. PLoS One (2013) 8(7):e67822. doi:10.1371/journal.pone.0067822
64. Nam HJ, van Deursen JM. Cyclin B2 and p53 control proper timing of centrosome separation. Nat Cell Biol (2014) 16(6):538-49. doi:10.1038/ncb2952
65. Andreassen PR, Lohez OD, Lacroix FB, Margolis RL. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell (2001) 12(5):1315-28. doi:10.1091/mbc.12.5.1315
66. Margolis RL, Lohez OD, Andreassen PR. G1 tetraploidy checkpoint and the suppression of tumorigenesis. J Cell Biochem (2003) 88(4):673-83. doi:10.1002/jcb.10411
67. Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature (2005) 437(7061):1043-7. doi:10.1038/nature04217
68. Gao F, Ponte JF, Levy M, Papageorgis P, Cook NM, Ozturk S, et al. hBub1 negatively regulates p53 mediated early cell death upon mitotic checkpoint activation. Cancer Biol Ther (2009) 8(7):548-56. doi:10.4161/cbt.8.7.7929
69. Fulco M, Costanzo A, Merlo P, Mangiacasale R, Strano S, Blandino G, et al. p73 is regulated by phosphorylation at the G2/M transition. J Biol Chem (2003) 278(49):49196-202. doi:10.1074/jbc.M304921200
70. Merlo P, Fulco M, Costanzo A, Mangiacasale R, Strano S, Blandino G, et al. A role of p73 in mitotic exit. J Biol Chem (2005) 280(34):30354-60. doi:10.1074/jbc.M500635200
71. Niikura Y, Dixit A, Scott R, Perkins G, Kitagawa K. BUB1 mediation of caspase-independent mitotic death determines cell fate. J Cell Biol (2007) 178(2):283-96. doi:10.1083/jcb.200702134
72. Toh WH, Nam SY, Sabapathy K. An essential role for p73 in regulating mitotic cell death. Cell Death Differ (2010) 17(5):787-800. doi:10.1038/cdd.2009.181
73. Marrazzo E, Marchini S, Tavecchio M, Alberio T, Previdi S, Erba E, et al. The expression of the DeltaNp73beta isoform of p73 leads to tetraploidy. Eur J Cancer (2009) 45(3):443-53. doi:10.1016/j.ejca.2008.09.024
74. Colaluca IN, Tosoni D, Nuciforo P, Senic-Matuglia F, Galimberti V, Viale G, et al. NUMB controls p53 tumour suppressor activity. Nature (2008) 451(7174):76-80. doi:10.1038/nature06412
75. Carter S, Vousden KH. A role for Numb in p53 stabilization. Genome Biol (2008) 9(5):221. doi:10.1186/gb-2008-9-5-221
76. Wirtz-Peitz F, Nishimura T, Knoblich JA. Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell (2008) 135(1):161-73. doi:10.1016/j.cell.2008.07.049
77. Bell GP, Fletcher GC, Brain R, Thompson BJ. Aurora kinases phosphorylate Lgl to induce mitotic spindle orientation in Drosophila epithelia. Curr Biol (2015) 25(1):61-8. doi:10.1016/j.cub.2014.10.052
78. Carvalho CA, Moreira S, Ventura G, Sunkel CE, Morais-de-Sa E. Aurora A triggers Lgl cortical release during symmetric division to control planar spindle orientation. Curr Biol (2015) 25(1):53-60. doi:10.1016/j.cub.2014.10.053
79. Siddique HR, Feldman DE, Chen CL, Punj V, Tokumitsu H, Machida K. NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. Hepatology (2015) 62(5):1466-79. doi:10.1002/hep.27987
80. D'Assoro AB, Liu T, Quatraro C, Amato A, Opyrchal M, Leontovich A, et al. The mitotic kinase Aurora-a promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERalpha(+) breast cancer cells. Oncogene (2014) 33(5):599-610. doi:10.1038/onc.2012.628
81. Zheng FM, Long ZJ, Hou ZJ, Luo Y, Xu LZ, Xia JL, et al. A novel small molecule Aurora kinase inhibitor attenuates breast tumor-initiating cells and overcomes drug resistance. Mol Cancer Ther (2014) 13(8):1991-2003. doi:10.1158/1535-7163.MCT-13-1029
82. Lee DF, Su J, Ang YS, Carvajal-Vergara X, Mulero-Navarro S, Pereira CF, et al. Regulation of embryonic and induced pluripotency by Aurora kinase-p53 signaling. Cell Stem Cell (2012) 11(2):179-94. doi:10.1016/j.stem.2012.05.020
83. Han MK, Song EK, Guo Y, Ou X, Mantel C, Broxmeyer HE. SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization. Cell Stem Cell (2008) 2(3):241-51. doi:10.1016/j.stem.2008.01.002
84. Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell (2003) 113(5):631-42. doi:10.1016/S0092-8674(03)00393-3
85. Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol (2005) 7(2):165-71. doi:10.1038/ncb1211
86. Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, et al. Dissecting self-renewal in stem cells with RNA interference. Nature (2006) 442(7102):533-8. doi:10.1038/nature04915
87. Li Z, Rana TM. A kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation. Nat Commun (2012) 3:1085. doi:10.1038/ncomms2059
88. Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, et al. Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci U S A (2003) 100(10):5974-9. doi:10.1073/pnas.0931261100
89. Ewart-Toland A, Briassouli P, de Koning JP, Mao JH, Yuan J, Chan F, et al. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nat Genet (2003) 34(4):403-12. doi:10.1038/ng1220
90. Weier HU, Mao JH. Meta-analysis of Aurora kinase A (AURKA) expression data reveals a significant correlation between increased AURKA expression and distant metastases in human ER-positive breast cancers. J Data Mining Genomics Proteomics (2013) 4(1):127. doi:10.4172/2153-0602.1000127
91. Opyrchal M, Salisbury JL, Zhang S, McCubrey J, Hawse J, Goetz MP, et al. Aurora-A mitotic kinase induces endocrine resistance through down-regulation of ERalpha expression in initially ERalpha+ breast cancer cells. PLoS One (2014) 9(5):e96995. doi:10.1371/journal.pone.0096995
92. Zhang D, Hirota T, Marumoto T, Shimizu M, Kunitoku N, Sasayama T, et al. Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models. Oncogene (2004) 23(54):8720-30. doi:10.1038/sj.onc.1208153
93. Wang X, Zhou YX, Qiao W, Tominaga Y, Ouchi M, Ouchi T, et al. Overexpression of Aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene (2006) 25(54):7148-58. doi:10.1038/sj.onc.1209707
94. Zhang D, Shimizu T, Araki N, Hirota T, Yoshie M, Ogawa K, et al. Aurora A overexpression induces cellular senescence in mammary gland hyperplastic tumors developed in p53-deficient mice. Oncogene (2008) 27(31):4305-14. doi:10.1038/onc.2008.76
95. Treekitkarnmongkol W, Katayama H, Kai K, Sasai K, Jones JC, Wang J, et al. Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer. Carcinogenesis (2016). doi:10.1093/carcin/bgw097
96. Torchia EC, Chen Y, Sheng H, Katayama H, Fitzpatrick J, Brinkley WR, et al. A genetic variant of Aurora kinase A promotes genomic instability leading to highly malignant skin tumors. Cancer Res (2009) 69(18):7207-15. doi:10.1158/0008-5472.CAN-09-1059