Kif14: A Clinically Relevant Kinesin and Potential Target for Cancer Therapy

  • Brigitte L. Thériault
  • Timothy W. CorsonEmail author


Kinesin family member 14 (KIF14) is an atypical N-3 kinesin identified as a potential oncogene in the prototypic genetic cancer retinoblastoma. KIF14 is crucial for the last phases of cytokinesis, where it interacts with protein regulating cytokinesis 1 (PRC1), citron kinase (CIT) and supervillin to mediate formation of the cleavage furrow. However its importance in cancer is perhaps better characterized than its cell biology, and has generated much interest in this kinesin as a potential prognostic marker and exciting therapeutic target. Located on chromosome 1q32.1, a common region of gain in many cancers, KIF14 demonstrates genomic gain and overexpression in multiple neoplasms. KIF14 expression is tumor-specific, and in breast, lung, ovarian, liver, and brain cancers expression correlates with stage, aggressiveness and poor patient outcomes. In cancer cells, KIF14 interacts with tumorigenic signaling pathways that promote cellular behaviors such as adhesion, invasion and chemotherapeutic resistance, with the end result of promoting tumor progression. Here we discuss the mounting evidence pointing to KIF14 as a prognostic marker and oncogenic stimulus in multiple cancers, as well as the additional evidence required for validation of KIF14 as a potential drug target.


Ovarian Cancer Ovarian Cancer Cell Line Papillary Renal Cell Carcinoma TNBC Cell Serous Ovarian Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Brenda Gallie (Ontario Cancer Institute) for critical comments on the manuscript. Related work in the laboratory of TWC has been supported by an American Cancer Society Institutional Research Grant, the Knights Templar Eye Foundation and the Alcon Research Institute. This publication was also made possible in part by Grant Number KL2TR001106 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award and by an unrestricted grant from Research to Prevent Blindness, Inc.


  1. 1.
    Thériault BL, Corson TW (2012) Kinesin family member 14 (KIF14). Atlas Genet Cytogenet Oncol Haematol 16:695–699Google Scholar
  2. 2.
    Durocher D et al (2000) The molecular basis of FHA domain: phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms. Mol Cell 6:1169–1182CrossRefPubMedGoogle Scholar
  3. 3.
    Dephoure N et al (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105:10762–10767CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Nomura N et al (1994) Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res 1:251–262CrossRefPubMedGoogle Scholar
  5. 5.
    Olsen JV et al (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127:635–648CrossRefPubMedGoogle Scholar
  6. 6.
    Vasilescu J et al (2007) The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells. J Proteome Res 6:298–305CrossRefPubMedGoogle Scholar
  7. 7.
    Miki H, Setou M, Kaneshiro K, Hirokawa N (2001) All kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci U S A 98:7004–7011CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Geer LY et al (2010) The NCBI BioSystems database. Nucleic Acids Res 38:D492–D496CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Ohkura H et al (1997) Mutation of a gene for a Drosophila kinesin-like protein, Klp38B, leads to failure of cytokinesis. J Cell Sci 110(Pt 8):945–954PubMedGoogle Scholar
  10. 10.
    Arora K et al (2014) KIF14 binds tightly to microtubules and adopts a rigor-like conformation. J Mol Biol 426:2997–3015CrossRefPubMedGoogle Scholar
  11. 11.
    Rice S (2014) Structure of Kif14: an engaging molecular motor. J Mol Biol 426:2993–2996CrossRefPubMedGoogle Scholar
  12. 12.
    Nakagawa T et al (1997) Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc Natl Acad Sci U S A 94:9654–9659CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Alphey L et al (1997) KLP38B: a mitotic kinesin-related protein that binds PP1. J Cell Biol 138:395–409CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Ruden DM, Cui W, Sollars V, Alterman M (1997) A Drosophila kinesin-like protein, Klp38B, functions during meiosis, mitosis, and segmentation. Dev Biol 191:284–296CrossRefPubMedGoogle Scholar
  15. 15.
    Molina I et al (1997) A chromatin-associated kinesin-related protein required for normal mitotic chromosome segregation in Drosophila. J Cell Biol 139:1361–1371CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Zhu C et al (2005) Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol Biol Cell 16:3187–3199CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Gruneberg U et al (2006) KIF14 and citron kinase act together to promote efficient cytokinesis. J Cell Biol 172:363–372CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Carleton M et al (2006) RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure. Mol Cell Biol 26:3853–3863CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Smith TC, Fang Z, Luna EJ (2010) Novel interactors and a role for supervillin in early cytokinesis. Cytoskeleton 67:346–364CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Watanabe S, De Zan T, Ishizaki T, Narumiya S (2013) Citron kinase mediates transition from constriction to abscission through its coiled-coil domain. J Cell Sci 126:1773–1784CrossRefPubMedGoogle Scholar
  21. 21.
    Bassi ZI, Audusseau M, Riparbelli MG, Callaini G, D’Avino PP (2013) Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc Natl Acad Sci U S A 110:9782–9787CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Samwer M et al (2013) The nuclear F-actin interactome of Xenopus oocytes reveals an actin-bundling kinesin that is essential for meiotic cytokinesis. EMBO J 32:1886–1902CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Fujikura K et al (2013) Kif14 mutation causes severe brain malformation and hypomyelination. PLoS One 8:e53490Google Scholar
  24. 24.
    Yunus J, Setsu T, Kikkawa S, Sakisaka T, Terashima T (2014) Cytoarchitecture of the olfactory bulb in the laggard mutant mouse. Neuroscience 275:259–271Google Scholar
  25. 25.
    Di Cunto F et al (2000) Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis. Neuron 28:115–127CrossRefPubMedGoogle Scholar
  26. 26.
    Filges I et al (2014) Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype. Clin Genet 86:220–228CrossRefPubMedGoogle Scholar
  27. 27.
    Corson TW, Huang A, Tsao MS, Gallie BL (2005) KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers. Oncogene 24:4741–4753CrossRefPubMedGoogle Scholar
  28. 28.
    Bell D et al (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615CrossRefGoogle Scholar
  29. 29.
    Wei X et al (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 43:442–446CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Wood LD et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318:1108–1113CrossRefPubMedGoogle Scholar
  31. 31.
    Bowles E et al (2007) Profiling genomic copy number changes in retinoblastoma beyond loss of RB1. Genes Chromosomes Cancer 46:118–129CrossRefPubMedGoogle Scholar
  32. 32.
    Kim TM et al (2008) Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q. Int J Cancer 123:2808–2815CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Thériault BL, Pajovic S, Bernardini MQ, Shaw PA, Gallie BL (2012) Kinesin family member 14: An independent prognostic marker and potential therapeutic target for ovarian cancer. Int J Cancer 130:1844–1854CrossRefPubMedGoogle Scholar
  34. 34.
    Wang Q et al (2013) Kinesin family member 14 is a candidate prognostic marker for outcome of glioma patients. Cancer Epidemiol 37:79–84CrossRefPubMedGoogle Scholar
  35. 35.
    Cam H et al (2004) A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell 16:399–411CrossRefPubMedGoogle Scholar
  36. 36.
    Thériault BL et al (2014) Transcriptional and epigenetic regulation of KIF14 overexpression in ovarian cancer. PLoS One 9:e91540CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Dimaras H et al (2008) Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma. Hum Mol Genet 17:1363–1372CrossRefPubMedGoogle Scholar
  38. 38.
    Szponar A, Zubakov D, Pawlak J, Jauch A, Kovacs G (2009) Three genetic developmental stages of papillary renal cell tumors: duplication of chromosome 1q marks fatal progression. Int J Cancer 124:2071–2076CrossRefPubMedGoogle Scholar
  39. 39.
    Pajovic S et al (2011) The TAg-RB murine retinoblastoma cell of origin has immunohistochemical features of differentiated Müller glia with progenitor properties. Invest Ophthalmol Vis Sci 52:7618–7624CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Singel SM et al (2014) KIF14 promotes AKT phosphorylation and contributes to chemoresistance in triple-negative breast cancer. Neoplasia 16:247–256, 256.e2CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Baudis M, Cleary ML (2001) an online repository for molecular cytogenetic aberration data. Bioinformatics 17:1228–1229CrossRefPubMedGoogle Scholar
  42. 42.
    Rhodes DR et al (2004) ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6:1–6CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Corson TW, Gallie BL (2006) KIF14 mRNA expression is a predictor of grade and outcome in breast cancer. Int J Cancer 119:1088–1094CrossRefPubMedGoogle Scholar
  44. 44.
    Corson TW et al (2007) KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer. Clin Cancer Res 13:3229–3234CrossRefPubMedGoogle Scholar
  45. 45.
    Yang T, Zhang XB, Zheng ZM (2013) Suppression of KIF14 expression inhibits hepatocellular carcinoma progression and predicts favorable outcome. Cancer Sci 104:552–557CrossRefPubMedGoogle Scholar
  46. 46.
    van’t Veer LJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536CrossRefGoogle Scholar
  47. 47.
    Madhavan J et al (2007) High expression of KIF14 in retinoblastoma: association with older age at diagnosis. Invest Ophthalmol Vis Sci 48:4901–4906CrossRefPubMedGoogle Scholar
  48. 48.
    Madhavan J et al (2009) KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association. Mol Vis 15:235–240PubMedCentralPubMedGoogle Scholar
  49. 49.
    Markowski J et al (2009) Gene expression profile analysis in laryngeal cancer by high-density oligonucleotide microarrays. J Physiol Pharmacol 60(Suppl 1):57–63PubMedGoogle Scholar
  50. 50.
    Markowski J et al (2009) Metal-proteinase ADAM12, kinesin 14 and checkpoint suppressor 1 as new molecular markers of laryngeal carcinoma. Eur Arch Otorhinolaryngol 266:1501–1507CrossRefPubMedGoogle Scholar
  51. 51.
    Xu H et al (2014) Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27Kip1 ubiquitination pathway in hepatocellular carcinoma. Exp Mol Med 46:e97CrossRefPubMedCentralPubMedGoogle Scholar
  52. 52.
    Mhawech-Fauceglia P et al (2010) Microarray analysis reveals distinct gene expression profiles among different tumor histology, stage and disease outcomes in endometrial adenocarcinoma. PLoS One 5:e15415CrossRefPubMedCentralPubMedGoogle Scholar
  53. 53.
    Lagarde P et al (2013) Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas. J Clin Oncol 31:608–615CrossRefPubMedGoogle Scholar
  54. 54.
    Singel SM et al (2013) A targeted RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate docetaxel chemosensitivity in triple-negative breast cancer. Clin Cancer Res 19:2061–2070CrossRefPubMedGoogle Scholar
  55. 55.
    Ehrlichova M et al (2013) The association of taxane resistance genes with the clinical course of ovarian carcinoma. Genomics 102:96–101CrossRefPubMedGoogle Scholar
  56. 56.
    Ahmed SM et al (2012) KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression. J Cell Biol 199:951–967CrossRefPubMedCentralPubMedGoogle Scholar
  57. 57.
    Thériault B, Dimaras H, Gallie B, Corson T (2014) The genomic landscape of retinoblastoma: a review. Clin Experiment Ophthalmol 42:33–52Google Scholar
  58. 58.
    Ewing RM et al (2007) Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol Syst Biol 3:89CrossRefPubMedCentralPubMedGoogle Scholar
  59. 59.
    Rath O, Kozielski F (2012) Kinesins and cancer. Nat Rev Cancer 12:527–539CrossRefPubMedGoogle Scholar
  60. 60.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefPubMedGoogle Scholar
  61. 61.
    Dai H et al (2007) Enhanced survival in perineural invasion of pancreatic cancer: an in vitro approach. Hum Pathol 38:299–307CrossRefPubMedGoogle Scholar
  62. 62.
    Abiatari I et al (2009) Consensus transcriptome signature of perineural invasion in pancreatic carcinoma. Mol Cancer Ther 8:1494–1504CrossRefPubMedGoogle Scholar
  63. 63.
    Hung PF et al (2013) The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma. PLoS One 8:e61664CrossRefPubMedCentralPubMedGoogle Scholar
  64. 64.
    Koide N et al (2006) Establishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin Cancer Res 12:2419–2426CrossRefPubMedGoogle Scholar
  65. 65.
    Basavarajappa HD, Corson TW (2012) KIF14 as an oncogene in retinoblastoma: a target for novel therapeutics? Future Med Chem 4:2149–2152CrossRefPubMedGoogle Scholar
  66. 66.
    Mao M, Linsley PS, Buser CA, Marshall CG, Kim AS (2004) Methods for identifying modulators of kinesin activity. WO 2004/109290 A2Google Scholar
  67. 67.
    Tanenbaum ME et al (2009) Kif15 cooperates with eg5 to promote bipolar spindle assembly. Curr Biol 19:1703–1711CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Campbell Family Cancer Research InstituteOntario Cancer Institute, Princess Margaret Cancer CentreTorontoCanada
  2. 2.Eugene and Marilyn Glick Eye Institute, Departments of Ophthalmology, Biochemistry and Molecular Biology, and Pharmacology and Toxicology, and Simon Cancer CenterIndiana University School of MedicineIndianapolisUSA

Personalised recommendations