Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype

Nature Communications

Volumn 7, Issue , 2016, Pages

  Zheng, Feimeng ^a   Yue, Caifeng ^a,b   Li, Guohui ^c   He, Bin ^a   Cheng, Wei ^a   Wang, Xi ^a   Yan, Min ^a   Long, Zijie ^b   Qiu, Wanshou ^b   Yuan, Zhongyu ^a   Xu, Jie ^a   Liu, Bing ^a   Shi, Qian ^d   Lam, Eric W F ^e   Hung, Mien Chie ^f,g,h   Liu, Quentin ^a,b  

^a SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^b SUN YAT SEN UNIVERSITY   (China)

^c DALIAN INSTITUTE OF CHEMICAL PHYSICS   (China)

^d FUDAN UNIVERSITY   (China)

^e IMPERIAL COLLEGE LONDON   (United Kingdom)

^f University of Texas MD Anderson Cancer Center ^*  (Taiwan)

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

^h CHINA MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AURORA A KINASE; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K; PHOSPHOTRANSFERASE; PHOSPHOTRANSFERASE INHIBITOR; TRANSCRIPTION FACTOR; MYC PROTEIN;

CANCER; CELLS AND CELL COMPONENTS; ENZYME ACTIVITY; INHIBITION; PHENOTYPE; TUMOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; CARCINOGENESIS; CONTROLLED STUDY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; ONCOGENE MYC; PHENOTYPE; PROMOTER REGION; STEM CELL; BREAST TUMOR; CANCER STEM CELL; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; FLOW CYTOMETRY; GENETICS; METABOLISM; MOLECULAR DYNAMICS; PHYSIOLOGY; RNA INTERFERENCE; TRANSPORT AT THE CELLULAR LEVEL; TUMOR CELL CULTURE; TUMOR CELL LINE;

AURORA KINASE A; BIOLOGICAL TRANSPORT; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; FLOW CYTOMETRY; HUMANS; MOLECULAR DYNAMICS SIMULATION; NEOPLASTIC STEM CELLS; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEINS C-MYC; RNA INTERFERENCE; TUMOR CELLS, CULTURED;

EID: 84955070264     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms10180     Document Type: Article

References (67)

1. Kitayama, H. et al. Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factordependent hematopoietic cell lines. Blood 85, 790-798 (1995).
2. Huw, L. Y. et al. Acquired PIK3CA amplification causes resistance to selective phosphoinositide 3-kinase inhibitors in breast cancer. Oncogenesis 2, e83 (2013).
3. Soda, M. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448, 561-566 (2007).
4. Weinstein, I. B., Joe, A. K. Mechanisms of disease: oncogene addiction-a rationale for molecular targeting in cancer therapy. Nat. Clin. Pract. Oncol. 3, 448-457 (2006).
5. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037 (2001).
6. Shaw, A. T. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med. 368, 2385-2394 (2013).
7. Katayama, R. et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci. Transl. Med. 4, 120-17 (2012).
8. Sharma, S. V., Bell, D. W., Settleman, J., Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7, 169-181 (2007).
9. Parker, W. T., Ho, M., Scott, H. S., Hughes, T. P., Branford, S. Poor response to second-line kinase inhibitors in chronic myeloid leukemia patients with multiple low-level mutations, irrespective of their resistance profile. Blood 119, 2234-2238 (2012).
10. Vermeulen, L., de Sousa e Melo, F., Richel, D. J., Medema, J. P. The developing cancer stem-cell model: clinical challenges and opportunities. Lancet Oncol. 13, e83-e89 (2012).
11. Chen, K., Huang, Y. H., Chen, J. L. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol. Sin. 34, 732-740 (2013).
12. Liu, P. P. et al. Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway. Cell Death Differ. 21, 124-135 (2014).
13. Munoz, P., Iliou, M. S., Esteller, M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol. Oncol. 6, 620-636 (2012).
14. Marumoto, T., Zhang, D., Saya, H. Aurora-A-a guardian of poles. Nat. Rev. Cancer 5, 42-50 (2005).
15. Kollareddy, M. et al. Aurora kinase inhibitors: progress towards the clinic. Invest. New Drugs 30, 2411-2432 (2012).
16. Goldberg, S. L. et al. An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes. Leuk. Res. Rep. 3, 58-61 (2014).
17. Otto, T. et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 15, 67-78 (2009).
18. Nikonova, A. S., Astsaturov, I., Serebriiskii, I. G., Dunbrack, Jr R. L., Golemis, E. A. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol. Life Sci. 70, 661-687 (2013).
19. Burum-Auensen, E. et al. Subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 assessed by immunohistochemistry. J. Histochem. Cytochem. 55, 477-486 (2007).
20. Lassus, H., Staff, S., Leminen, A., Isola, J., Butzow, R. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma. Gynecol. Oncol. 120, 11-17 (2011).
21. Tatsuka, M. et al. Oncogenic role of nuclear accumulated Aurora-A. Mol. Carcinog. 48, 810-820 (2009).
22. Anand, S., Penrhyn-Lowe, S., Venkitaraman, A. R. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 3, 51-62 (2003).
23. Cammareri, P. et al. Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res. 70, 4655-4665 (2010).
24. Sun, H. et al. Aurora-A controls cancer cell radio-and chemoresistance via ATM/Chk2-mediated DNA repair networks. Biochim. Biophys. Acta 1843, 934-944 (2014).
25. D'Assoro, A. B. et al. The mitotic kinase Aurora-a promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERalpha(\+) breast cancer cells. Oncogene 33, 599-610 (2014).
26. Yan, M., Liu, Q. Q. Targeted therapy: tailoring cancer treatment. Chin. J. Cancer 32, 363-364 (2013).
27. Xu, J. et al. Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer. PLoS ONE 8, e56919 (2013).
28. Siggelkow, W. et al. Expression of aurora kinase A is associated with metastasisfree survival in node-negative breast cancer patients. BMC Cancer 12, 562 (2012).
29. Ginestier, C. et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1, 555-567 (2007).
30. Crosio, C. et al. Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol. Cell. Biol. 22, 874-885 (2002).
31. Katayama, H. et al. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat. Genet. 36, 55-62 (2004).
32. Piskacek, S. et al. Nine-amino-acid transactivation domain: establishment and prediction utilities. Genomics 89, 756-768 (2007).
33. Venot, C., Maratrat, M., Sierra, V., Conseiller, E., Debussche, L. Definition of a p53 transactivation function-deficient mutant and characterization of two independent p53 transactivation subdomains. Oncogene 18, 2405-2410 (1999).
34. Szklarczyk, D. et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39, D561-D568 (2011).
35. Meyer, N., Penn, L. Z. Reflecting on 25 years with MYC. Nat. Rev. Cancer 8, 976-990 (2008).
36. Wierstra, I., Alves, J. The c-myc promoter: still MysterY and challenge. Adv. Cancer Res. 99, 113-333 (2008).
37. Ong, S. E. et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol. Cell. Proteomics 1, 376-386 (2002).
38. Hsueh, K. W., Fu, S. L., Huang, C. Y., Lin, C. H. Aurora-A phosphorylates hnRNPK and disrupts its interaction with p53. FEBS Lett. 585, 2671-2675 (2011).
39. Michael, W. M., Eder, P. S., Dreyfuss, G. The K nuclear shuttling domain: a novel signal for nuclear import and nuclear export in the hnRNP K protein. EMBO J. 16, 3587-3598 (1997).
40. Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899-905 (2010).
41. Polack, A., Feederle, R., Klobeck, G., Hortnagel, K. Regulatory elements in the immunoglobulin kappa locus induce c-myc activation and the promoter shift in Burkitt's lymphoma cells. EMBO J. 12, 3913-3920 (1993).
42. Broome, H. E., Reed, J. C., Godillot, E. P., Hoover, R. G. Differential promoter utilization by the c-myc gene in mitogen-and interleukin-2-stimulated human lymphocytes. Mol. Cell. Biol. 7, 2988-2993 (1987).
43. Ruppert, C., Goldowitz, D., Wille, W. Proto-oncogene c-myc is expressed in cerebellar neurons at different developmental stages. EMBO J. 5, 1897-1901 (1986).
44. Takimoto, M. et al. Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. J. Biol. Chem. 268, 18249-18258 (1993).
45. DesJardins, E., Hay, N. Repeated CT elements bound by zinc finger proteins control the absolute and relative activities of the two principal human c-myc promoters. Mol. Cell. Biol. 13, 5710-5724 (1993).
46. Michelotti, E. F., Tomonaga, T., Krutzsch, H., Levens, D. Cellular nucleic acid binding protein regulates the CT element of the human c-myc protooncogene. J. Biol. Chem. 270, 9494-9499 (1995).
47. Dar, A. A., Belkhiri, A., El-Rifai, W. The aurora kinase A regulates GSK-3beta in gastric cancer cells. Oncogene 28, 866-875 (2009).
48. Ho, J. S., Ma, W., Mao, D. Y., Benchimol, S. p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol. Cell. Biol. 25, 7423-7431 (2005).
49. Zheng, F. M. et al. A novel small molecule aurora kinase inhibitor attenuates breast tumor-initiating cells and overcomes drug resistance. Mol. Cancer Ther. 13, 1991-2003 (2014).
50. Dutertre, S., Descamps, S., Prigent, C. On the role of aurora-A in centrosome function. Oncogene 21, 6175-6183 (2002).
51. Braun, A. et al. Rac1 and Aurora A regulate MCAK to polarize microtubule growth in migrating endothelial cells. J. Cell Biol. 206, 97-112 (2014).
52. Wirtz-Peitz, F., Nishimura, T., Knoblich, J. A. Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell 135, 161-173 (2008).
53. Regan, J. L. et al. Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner. Cell Rep. 4, 110-123 (2013).
54. Kimura, M. T. et al. Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk. Cancer Res. 65, 3548-3554 (2005).
55. Brockmann, M. et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell 24, 75-89 (2013).
56. Detre, S., Saclani Jotti, G., Dowsett, M. A 'quickscore' method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J. Clin. Pathol. 48, 876-878 (1995).
57. Fancelli, D. et al. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. J. Med. Chem. 49, 7247-7251 (2006).
58. Hess, B., Kutzner, C., Spoel, D. V. D., Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447 (2008).
59. Oostenbrink, C., Villa, A., Mark, A. E., van Gunsteren, W. F. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J. Comput. Chem. 25, 1656-1676 (2004).
60. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926-935 (1983).
61. Hess, B., Bekker, H., Berendsen, H. J. C., Fraaije, JGEM. LINCS: A linear constraint solver for molecular simulations. J. Comp. Chem. 18, 1463-1472 (1997).
62. Essmann, U., Perera, L., Berkowitz, M. L. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577-8593 (1995).
63. Lee, D. F. et al. Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling. Cell Stem Cell 11, 179-194 (2012).
64. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545-15550 (2005).
65. Creighton, C. J. et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc. Natl Acad. Sci. USA 106, 13820-13825 (2009).
66. Schuhmacher, M. et al. The transcriptional program of a human B cell line in response to Myc. Nucleic Acids Res. 29, 397-406 (2001).
67. Zeller, K. I., Jegga, A. G., Aronow, B. J., O'Donnell, K. A., Dang, C. V. An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol. 4, R69 (2003).