Role of NEK2A in human cancer and its therapeutic potentials

BioMed Research International

Volumn 2015, Issue , 2015, Pages

  Xia, Jiliang ^a   Franqui Machin, Reinaldo ^b   Gu, Zhimin ^b   Zhan, Fenghuang ^b  

^a SOUTHERN MEDICAL UNIVERSITY   (China)

^b UNIVERSITY OF IOWA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NEVER IN MITOSIS RELATED KINASE 2A; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG; NEK2 PROTEIN, HUMAN;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANEUPLOIDY; ARTICLE; ASPERGILLUS NIDULANS; BILE DUCT CARCINOMA; BLADDER CARCINOMA; BREAST CANCER; BREAST CARCINOMA; CANCER CELL LINE; CANCER RESISTANCE; CARCINOGENESIS; CELL FUNCTION; CELLULAR DISTRIBUTION; CENTROSOME; CHROMOSOME 1; COLON CARCINOMA; COLORECTAL CANCER; DRUG RESISTANCE; EWING SARCOMA; GENOMIC INSTABILITY; GLIOBLASTOMA; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG ADENOCARCINOMA; MALIGNANT PERIPHERAL NERVE SHEATH TUMOR; MANTLE CELL LYMPHOMA; MELANOMA; MESOTHELIOMA; MITOSIS; MULTIPLE MYELOMA; MYELOID LEUKEMIA; NEOPLASM; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY ADENOCARCINOMA; PANCREAS ADENOCARCINOMA; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROCESSING; RNA SPLICING; SEMINOMA; TUMOR GROWTH; UTERINE CERVIX CANCER; CELL PROLIFERATION; GENE EXPRESSION REGULATION; GENETICS; METASTASIS; NEOPLASMS; PATHOLOGY;

CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MITOSIS; NEOPLASM METASTASIS; NEOPLASMS; PROTEIN-SERINE-THREONINE KINASES;

EID: 84924127006     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2015/862461     Document Type: Article

References (90)

1. C. Lengauer, K.W. Kinzler, and B. Vogelstein, "Genetic instabilities in human cancers," Nature, vol. 396, no. 6712, pp. 643-649, 1998.
2. S. L. Thompson, S. F. Bakhoum, and D. A. Compton, "Mechanisms of chromosomal instability," Current Biology, vol. 20, no. 6, pp. R285-R295, 2010.
3. M. A. Nowak, N. L. Komarova, A. Sengupta et al., "The role of chromosomal instability in tumor initiation," Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 25, pp. 16226-16231, 2002.
4. K. Fukasawa, "Centrosome amplification, chromosome instability and cancer development," Cancer Letters, vol. 230, no. 1, pp. 6-19, 2005.
5. S. F. Bakhoum and D. A. Compton, "Chromosomal instability and cancer: a complex relationship with therapeutic potential," The Journal of Clinical Investigation, vol. 122, no.4,pp. 1138-1143, 2012.
6. T. Boveri, " Über mehrpolige mitosen als mittel zur analyse des zellkerns," Verhandlungen der Physikalisch-Medizinische Gesellschaft, vol. 35, pp. 67-90, 1902.
7. S.M. Gollin, "Mechanisms leading to chromosomal instability," Seminars in Cancer Biology, vol. 15, no. 1, pp. 33-42, 2005.
8. N. J. Ganem, S. A. Godinho, and D. Pellman, "A mechanism linking extra centrosomes to chromosomal instability," Nature, vol. 460, no. 7252, pp. 278-282, 2009.
9. G. de Ćarcer and M. Malumbres, "A centrosomal route for cancer genome instability," Nature Cell Biology, vol. 16, no. 6, pp. 504-506, 2014.
10. J.-M. Schvartzman, R. Sotillo, and R. Benezra, "Mitotic chromosomal instability and cancer:mouse modelling of the human disease," Nature Reviews Cancer, vol. 10, no. 2, pp. 102-115, 2010.
11. J. J. Li and S. A. Li, "Mitotic kinases: the key to duplication, segregation, and cytokinesis errors, chromosomal instability, and oncogenesis," Pharmacology and Therapeutics, vol. 111, no. 3, pp. 974-984, 2006.
12. W. Zhou, Y. Yang, J. Xia et al., "NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers," Cancer Cell, vol. 23, no. 1, pp. 48-62, 2013.
13. D. G. Hayward and A. M. Fry, "Nek2 kinase in chromosome instability and cancer," Cancer Letters, vol. 237, no. 2, pp. 155-166, 2006.
14. S. J. Schultz, A. M. Fry, C. Sutterlin, T. Ried, and E. A.Nigg, "Cell cycle-dependent expression of Nek2, a novel human protein kinase related to the NIMA mitotic regulator of Aspergillus nidulans," Cell Growth and Differentiation, vol. 5, no. 6, pp. 625-635, 1994.
15. P. Rellos, F. J. Ivins, J. E. Baxter et al., "Structure andregulationof the human Nek2 centrosomal kinase," The Journal of Biological Chemistry, vol. 282, no. 9, pp. 6833-6842, 2007.
16. H. K. Yong, Y. C. Jun, Y. Jeong, D. J.Wolgemuth, and K. Rhee, "Nek2 localizes to multiple sites in mitotic cells, suggesting its involvement inmultiple cellular functions during the cell cycle," Biochemical and Biophysical Research Communications, vol. 290, no. 2, pp. 730-736, 2002.
17. A. M. Fry, P. Meraldi, and E. A. Nigg, "A centrosomal function for the human Nek2 protein kinase, a member of the NIMA family of cell cycle regulators," The EMBO Journal, vol. 17, no. 2, pp. 470-481, 1998.
18. K. Rhee and D. J. Wolgemuth, "The NIMA-related kinase 2, Nek2, is expressed in specific stages of themeiotic cell cycle and associates with meiotic chromosomes," Development, vol. 124, no. 11, pp. 2167-2177, 1997.
19. T. Fujioka, Y. Takebayashi,M. Ito, and T. Uchida, "Nek2 expression and localization in porcine oocyte during maturation," Biochemical and Biophysical Research Communications, vol. 279, no. 3, pp. 799-802, 2000.
20. R. S. Hames, R. E. Crookes, K. R. Straatman et al., "Dynamic recruitment of Nek2 kinase to the centrosome involves microtubules, PCM-1, and localized proteasomal degradation," Molecular Biology of the Cell, vol. 16, no. 4, pp. 1711-1724, 2005.
21. A. M. Fry, S. J. Schultz, J. Bartek, and E. A. Nigg, "Substrate specificity and cell cycle regulation of the Nek2 protein kinase, a potential human homolog of the mitotic regulator NIMA of Aspergillus nidulans," The Journal of Biological Chemistry, vol. 270, no. 21, pp. 12899-12905, 1995.
22. R. S. Hames, S. L.Wattam, H. Yamano, R. Bacchieri, and A. M. Fry, "APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin Atype D-box," The EMBO Journal, vol. 20, no. 24, pp. 7117-7127, 2002.
23. G. G. Sedgwick, D. G. Hayward, B. di Fiore et al., "Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex," The EMBO Journal, vol. 32, no. 2, pp. 303-314, 2013.
24. B. Ren, H. Cam, Y. Takahashi et al., "E2F integrates cell cycle progression with DNA repair, replication, and G2/M checkpoints," Genes and Development, vol. 16, no. 2, pp. 245-256, 2002.
25. A. M. Fry, L. Arnaud, and E. A. Nigg, "Activity of the human centrosomal kinase, Nek2, depends on an unusual leucine zipper dimerization motif,"The Journal of Biological Chemistry, vol. 274, no. 23, pp. 16304-16310, 1999.
26. N. R. Helps, X. Luo, H. M. Barker, and P. T.W. Cohen, "NIMArelated kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1," Biochemical Journal, vol. 349, no. 2, pp. 509-518, 2000.
27. J. Mi, C. Guo, D. L. Brautigan, and J. M. Larner, "Protein phosphatase-1 regulates centrosome splitting through Nek2," Cancer Research, vol. 67, no. 3, pp. 1082-1089, 2007.
28. A. M. Fry, T.Mayor, P.Meraldi, Y. D. Stierhof, K. Tanaka, and E. A. Nigg, "C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2," Journal of Cell Biology, vol. 141, no. 7, pp. 1563-1574, 1998.
29. S. Bahe, Y.-D. Stierhof, C. J. Wilkinson, F. Leiss, and E. A. Nigg, "Rootletin forms centriole-associated filaments and functionsin centrosome cohesion,"The Journal of Cell Biology, vol. 171, no. 1, pp. 27-33, 2005.
30. A. J. Faragher and A. M. Fry, "Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles,"Molecular Biology of the Cell, vol. 14, no. 7, pp. 2876-2889, 2003.
31. R. Gräf, "DdNek2, the first non-vertebrate homologue of human Nek2, is involved in the formation of microtubuleorganizing centers," Journal of Cell Science, vol. 115, no. 9, pp. 1919-1929, 2002.
32. J. Rapley, J. E. Baxter, J. Blot et al., "Coordinate regulation of the mother centriole component Nlp by Nek2 and Plk1 protein kinases,"Molecular and Cellular Biology, vol. 25,no. 4, pp. 1309-1324, 2005.
33. Y. Jeong, J. Lee, K.Kim, J. C.Yoo, andK. Rhee, "Characterization of NIP2/centrobin, a novel substrate of Nek2, and its potential role in microtubule stabilization," Journal of Cell Science, vol. 120, no. 12, pp. 2106-2116, 2007.
34. S. Sonn, Y. Jeong, and K. Rhee, "Nip2/centrobin may be a substrate of Nek2 that is required for proper spindle assembly during mitosis in early mouse embryos," Molecular Reproduction and Development, vol. 76, no. 6, pp. 587-592, 2009.
35. S. Sonn, G. T. Oh, and K. Rhee, "Nek2 and its substrate, centrobin/Nip2, are required for proper meiotic spindle formation of the mouse oocytes," Zygote, vol. 19, no. 1, pp. 15-20, 2011.
36. S. Grisendi, C. Mecucci, B. Falini, and P. P. Pandolfi, "Nucleophosmin and cancer," Nature Reviews Cancer, vol. 6, no. 7, pp. 493-505, 2006.
37. J. Yao, C. Fu, X. Ding et al., "Nek2A kinase regulates the localization of numatrin to centrosome inmitosis," FEBS Letters, vol. 575, no. 1-3, pp. 112-118, 2004.
38. S. di Agostino, M. Fedele, P. Chieffi et al., "Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first meiotic division in mouse spermatocytes," Molecular Biology of the Cell, vol. 15, no. 3, pp. 1224-1232, 2004.
39. S.Di Agostino, P. Rossi, R. Geremia, and C. Sette, "The MAPK pathway triggers activation of Nek2 during chromosome condensation in mouse spermatocytes," Development, vol. 129, no. 7, pp. 1715-1727, 2002.
40. Y. Lou, J. Yao, A. Zereshki et al., "NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling,"The Journal of Biological Chemistry, vol. 279, no. 19, pp. 20049-20057, 2004.
41. G. Prime and D. Markie, "The telomere repeat binding protein Trf1 interacts with the spindle checkpoint protein Mad1 and Nek2 mitotic kinase," Cell Cycle, vol. 4, no. 1, pp. 121-124, 2005.
42. R. Wei, B. Ngo, G. Wu, and W. H. Lee, "Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint," Molecular Biology of the Cell, vol. 22, no. 19, pp. 3584-3594, 2011.
43. G. Fu, X. Ding, K. Yuan et al., "Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression inmitosis," Cell Research, vol. 17, no. 7, pp. 608-618, 2007.
44. C. Naro, F. Barbagallo, P. Chieffi, C. F. Bourgeois, M. P. Paronetto, and C. Sette, "The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival," Nucleic Acids Research, vol. 42, no. 5, pp. 3218-3227, 2014.
45. D. H. Wai, K.-L. Schaefer, A. Schramm et al., "Expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays," International Journal of Oncology, vol. 20, no. 3, pp. 441-451, 2002.
46. T. Kokuryo, T. Senga, Y. Yokoyama, M. Nagino, Y. Nimura, and M. Hamaguchi, "Nek2 as an effective target for inhibition of tumorigenic growth and peritoneal dissemination of cholangiocarcinoma," Cancer Research, vol. 67, no. 20, pp. 9637-9642, 2007.
47. F. Barbagallo, M. P. Paronetto, R. Franco et al., "Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas,"TheJournal of Pathology, vol. 217, no. 3, pp. 431-441, 2009.
48. N. Tsunoda, T. Kokuryo, K. Oda et al., "Nek2 as a novel molecular target for the treatment of breast carcinoma," Cancer Science, vol. 100, no. 1, pp. 111-116, 2009.
49. S.Wang,W. Li, N. Liu et al., "Nek2A contributes to tumorigenic growth and possibly functions as potential therapeutic target for human breast cancer," Journal of Cellular Biochemistry, vol. 113, no. 6, pp. 1904-1914, 2012.
50. D. G. Hayward, R. B. Clarke, A. J. Faragher, M. R. Pillai, I. M. Hagan, and A. M. Fry, "The centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer," Cancer Research, vol. 64, no. 20, pp. 7370-7376, 2004.
51. S.Wang,W. Li, S. Lv et al., "Abnormal expression ofNek2 and catenin in breast carcinoma: clinicopathological correlations," Histopathology, vol. 59, no. 4, pp. 631-642, 2011.
52. M. Marina and H. Saavedra, "Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance," Frontiers in Bioscience, vol. 19, pp. 352-365, 2014.
53. K. Suzuki, T. Kokuryo, T. Senga, Y. Yokoyama,M.Nagino, and M. Hamaguchi, "Novel combination treatment for colorectal cancer usingNek2 siRNAand cisplatin,"Cancer Science, vol. 101, no. 5, pp. 1163-1169, 2010.
54. C. P.Neal, A. M. Fry, C. Moreman et al., "Overexpression of the Nek2 kinase in colorectal cancer correlates with beta-catenin relocalization and shortened cancer-specific survival," Journal of Surgical Oncology, vol. 110, no. 7, pp. 828-838, 2014.
55. T. P. Stricker, K. J. Henriksen, J. H. Tonsgard, A. G. Montag, T. N.Krausz, and P. Pytel, "Expression profiling of 519 kinase genes in matchedmalignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation," Modern Pathology, vol. 26, no. 7, pp. 930-943, 2013.
56. X. Zhong, X. Guan, Q. Dong et al., "Examining Nek2 as a better proliferation marker in non-small cell lung cancer prognosis," Tumor Biology, vol. 35, no. 7, pp. 7155-7162, 2014.
57. Y. Cheng, M. Hong, and B. Cheng, "Identified differently expressed genes in renal cell carcinoma by using multiple microarray datasets running head: differently expressed genes in renal cell carcinoma," European Review for Medical and Pharmacological Sciences, vol. 18, no. 7, pp. 1033-1040, 2014.
58. Z. Ning, A. Wang, J. Liang et al., "Abnormal expression of Nek2 in pancreatic ductal adenocarcinoma: a novel marker for prognosis," International Journal of Clinical and Experimental Pathology, vol. 7, no. 5, pp. 2462-2469, 2014.
59. B. R. Mardin, C. Lange, J. E. Baxter et al., "Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction," Nature Cell Biology, vol. 12, no. 12, pp. 1166-1176, 2010.
60. B. R.Mardin, F. G.Agircan, C. Lange, and E. Schiebel, "Plk1 controls the Nek2A-PP1 antagonism in centrosome disjunction," Current Biology, vol. 21, no. 13, pp. 1145-1151, 2011.
61. B. C.Mbom, K. A. Siemers, M. A. Ostrowski, W. J. Nelson, and A. I. M. Barth, "Nek2 phosphorylates and stabilizes cateninat mitotic centrosomes downstream of Plk1," Molecular Biology of the Cell, vol. 25, no. 7, pp. 977-991, 2014.
62. M. K. H. Pitner and H. I. Saavedra, "Cdk4 and nek2 signal binucleation and centrosome amplification in a her2+ breast cancer model," PLoS ONE, vol. 8, no. 6,Article ID e65971, 2013.
63. Q. Liu, Y. Hirohashi, X. Du, M. I. Greene, and Q. Wang, "Nek2 targets themitotic checkpoint proteinsMad2 and Cdc20: a mechanism for aneuploidy in cancer," Experimental and Molecular Pathology, vol. 88, no. 2, pp. 225-233, 2010.
64. J. Lee and L. Gollahon, "Mitotic perturbations induced by Nek2 overexpression require interaction with TRF1 in breast cancer cells," Cell Cycle, vol. 12, no. 23, pp. 3599-3614, 2013.
65. P. Cappello, H. Blaser, C. Gorrini et al., "Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells," Oncogene, vol. 33, no. 18, pp. 2375-2384, 2014.
66. A. M. Fry and E. A. Nigg, "Characterization of mammalian NIMA-related kinases," Methods in Enzymology, vol. 283, pp. 270-282, 1997.
67. U. Andreasson,M. Dictor, M. Jerkeman et al., "Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells," The American Journal of Hematology, vol. 84, no. 12, pp. 803-808, 2009.
68. Y. Takahashi, T. Iwaya, G. Sawada et al., "Up-regulation of NEK2 by MicroRNA-128 methylation is associated with poor prognosis in colorectal cancer," Annals of Surgical Oncology, vol. 21, no. 1, pp. 205-212, 2014.
69. N. H. Nabilsi, D. J. Ryder, A. C. Peraza-Penton, R. Poudyal, D. S. Loose, and M. P. Kladde, "Local depletion of DNA methylation identifies a repressive p53 regulatory region in the NEK2 promoter," The Journal of Biological Chemistry, vol. 288, no. 50, pp. 35940-35951, 2013.
70. D. Patel, A. Incassati, N. Wang, and D. J. McCance, "Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G 2-M-phase proteins," Cancer Research, vol. 64, no. 4, pp. 1299-1306, 2004.
71. D. R. Wonsey and M. T. Follettie, "Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe," Cancer Research, vol. 65, no. 12, pp. 5181-5189, 2005.
72. J.-H. Dannenberg, L. Schuijff, M. Dekker, M. Van Der Valk, and H. Te Riele, "Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130," Genes and Development, vol. 18, no. 23, pp. 2952-2962, 2004.
73. R. Fodde, R. Smits, and H. Clevers, "APC, signal transduction and genetic instability in colorectal cancer," Nature Reviews Cancer, vol. 1, no. 1, pp. 55-67, 2001.
74. A. Ahmad, Z. Wang, D. Kong et al., "FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors," Breast Cancer Research and Treatment, vol. 122, no. 2, pp. 337-346, 2010.
75. M. Narisawa-Saito and T. Kiyono, "Basic mechanisms of highrisk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins," Cancer Science, vol. 98, no. 10, pp. 1505-1511, 2007.
76. H. I. Saavedra, K. Fukasawa, C. W. Conn, and P. J. Stambrook, "MAPK mediates RAS-induced chromosome instability," The Journal of Biological Chemistry, vol. 274, no. 53, pp. 38083-38090, 1999.
77. Y. Yamamoto, H. Matsuyama, S. Kawauchi et al., "Overexpression of polo-like kinase 1 (PLK1) and chromosomal instability in bladder cancer," Oncology, vol. 70, no. 3, pp. 231-237, 2006.
78. E. Diaz-Rodŕguez, R. Sotillo, J.-M. Schvartzman, and R. Benezra, "Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo," Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 43, pp. 16719-16724, 2008.
79. T. K. Das, D. Dana, S. S. Paroly et al., "Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis," Oncogenesis, vol. 2, article e69, 2013.
80. X. Liu, Y. Gao, Y. Lu, J. Zhang, L. Li, and F. Yin, "Upregulation of NEK2 is associated with drug resistance in ovarian cancer," Oncology Reports, vol. 31, no. 2, pp. 745-754, 2014.
81. R. Mathew, V. Karantza-Wadsworth, and E. White, "Role of autophagy in cancer," Nature Reviews Cancer, vol. 7, no. 12, pp. 961-967, 2007.
82. B. Hoang, A. Benavides, Y. Shi, P. Frost, and A. Lichtenstein, "Effect of autophagy on multiple myeloma cell viability," Molecular Cancer Therapeutics, vol. 8, no. 7, pp. 1974-1984, 2009.
83. D. G. Hayward, Y. Newbatt, L. Pickard et al., "Identification by high-throughput screening of viridin analogs as biochemical and cell-based inhibitors of the cell cycle-regulated Nek2 kinase," Journal of Biomolecular Screening, vol. 15,no. 8, pp. 918-927, 2010.
84. P. Innocenti, K.-M. J. Cheung, S. Solanki et al., "Design of potent and selective hybrid inhibitors of themitotic kinase nek2: structure-activity relationship, structural biology, and cellular activity," Journal ofMedicinal Chemistry, vol. 55, no. 7, pp. 3228-3241, 2012.
85. X.-L. Qui, G. Li, G. Wu et al., "Synthesis and biological evaluation of a series of novel inhibitor of Nek2/Hec1 analogues," Journal of Medicinal Chemistry, vol. 52, no. 6, pp. 1757-1767, 2009.
86. H. Lebraud, C. R. Coxon, V. S. Archard et al., "Model systemfor irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles," Organic and Biomolecular Chemistry, vol. 12, no. 1, pp. 141-148, 2014.
87. G. Wu, X.-L. Qiu, L. Zhou et al., "Small molecule targeting the Hec1/Nek2 mitotic pathway suppresses tumor cell growth in culture and in animal," Cancer Research, vol. 68, no. 20, pp. 8393-8399, 2008.
88. C.-M. Hu, J. Zhu, X. E. Guo et al., "Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trapmechanism," Oncogene, 2014.
89. L. Y. Huang, Y.-S. Lee, J.-J. Huang et al., "Characterization of the biological activity of a potent small molecule Hec1 inhibitor TAI-1," Journal of Experimental and Clinical Cancer Research, vol. 33, article 6, 2014.
90. L. Y. Huang, C. C. Chang, Y. S. Lee et al., "Inhibition of Hec1 as a novel approach for treatment of primary liver cancer," Cancer Chemotherapy and Pharmacology, vol. 74, no. 3, pp. 511-520, 2014.