Skip to main content
SpringerLink
Log in

KIF20A, highly expressed in immature hematopoietic cells, supports the growth of HL60 cell line

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

A microtubule-associated motor protein, kinesin-like family member 20A (KIF20A; also called MKlp2) is required for cytokinesis and contributes to intracellular vesicular trafficking. KIF20A plays a critical role in the development of several cancers, but its role in blood cells and hematological malignancies have not been studied. In the present study, we focused on the role of KIF20A in hematopoietic cells and possible involvement in myeloid neoplasms. We found that human leukemia cell lines and normal bone marrow CD34-positive cells stimulated by growth factors, but not mature peripheral blood cells, exhibit high KIF20A expression. We further found that HL60 cells, which originally express a large amount of KIF20A, showed decreased KIF20A expression in parallel with both neutrophil-like and macrophage-like differentiation-induction. KIF20A-knockdown using a lentivirus shRNA transfection system led to partial cell cycle arrest at the G2/M phase and frequent appearance of multinucleated cells. Treatment with a KIF20A-selective inhibitor, paprotrain enhanced the multinuclearity of KIF20A-knockdown cell clones and suppressed growth. The present study contributes to our understanding of the role of KIF20A in blood cells and leukemia cells in particular.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lai F, Fernald AA, Zhao N, Le Beau MM. cDNA cloning, expression pattern, genomic structure and chromosomal location of RAB6KIFL, a human kinesin-like gene. Gene. 2000;248:117–25.

    Article  CAS  Google Scholar 

  2. Fontijn RD, Goud B, Echard A, Jollivet F, van Marle J, Pannekoek H, et al. The human kinesin-like protein RB6K is under tight cell cycle control and is essential for cytokinesis. Mol Cell Biol. 2001;21:2944–55.

    Article  CAS  Google Scholar 

  3. Gruneberg U, Neef R, Honda R, Nigg EA, Barr FA. Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2. J Cell Biol. 2004;166:167–72.

    Article  CAS  Google Scholar 

  4. Neef R, Klein UR, Kopajtich R, Barr FA. Cooperation between mitotic kinesins controls the late stages of cytokinesis. Curr Biol. 2006;16:301–7.

    Article  CAS  Google Scholar 

  5. Lee SH, McCormick F, Saya H. Mad2 inhibits the mitotic kinesin MKlp2. J Cell Biol. 2010;191:1069–77.

    Article  CAS  Google Scholar 

  6. Gasnereau I, Boissan M, Margall-Ducos G, Couchy G, Wendum D, Bourgain-Guglielmetti F, et al. KIF20A mRNA and its product MKlp2 are increased during hepatocyte proliferation and hepatocarcinogenesis. Am J Pathol. 2012;180:131–40.

    Article  CAS  Google Scholar 

  7. Kitagawa M, Fung SY, Hameed UF, Goto H, Inagaki M, Lee SH. Cdk1 coordinates timely activation of MKlp2 kinesin with relocation of the chromosome passenger complex for cytokinesis. Cell Rep. 2014;7:166–79.

    Article  CAS  Google Scholar 

  8. Zhang Y, Liu J, Peng X, Zhu CC, Han J, Luo J, et al. KIF20A regulates porcine oocyte maturation and early embryo development. PLoS One. 2014;9:e102898.

    Article  Google Scholar 

  9. Taniuchi K, Nakagawa H, Nakamura T, Eguchi H, Ohigashi H, Ishikawa O, et al. Down-regulation of RAB6KIFL/KIF20A, a kinesin involved with membrane trafficking of discs large homologue 5, can attenuate growth of pancreatic cancer cell. Cancer Res. 2005;65:105–12.

    Article  CAS  Google Scholar 

  10. Taniuchi K, Furihata M, Saibara T. KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells. Neoplasia. 2014;16:1082–93.

    Article  CAS  Google Scholar 

  11. Duan J, Huang W, Shi H. Positive expression of KIF20A indicates poor prognosis of glioma patients. Onco Targets Ther. 2016;9:6741–9.

    Article  CAS  Google Scholar 

  12. Zhang W, He W, Shi Y, Gu H, Li M, Liu Z, et al. High expression of KIF20A is associated with poor overall survival and tumor progression in early-stage cervical squamous cell carcinoma. PLoS One. 2016;11:e0167449.

    Article  Google Scholar 

  13. Liu SL, Lin HX, Qiu F, Zhang WJ, Niu CH, Wen W, et al. Overexpression of kinesin family member 20A correlates with disease progression and poor prognosis in human nasopharyngeal cancer: a retrospective analysis of 105 patients. PLoS One. 2017;12:e0169280.

    Article  Google Scholar 

  14. Suzuki N, Hazama S, Ueno T, Matsui H, Shindo Y, Iida M, et al. A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer. J Immunother. 2014;37:36–42.

    Article  CAS  Google Scholar 

  15. Komrokji RS, List AF. Short- and long-term benefits of lenalidomide treatment in patients with lower-risk del(5q) myelodysplastic syndromes. Ann Oncol. 2016;27:62–8.

    Article  CAS  Google Scholar 

  16. Matsuoka A, Tochigi A, Kishimoto M, Nakahara T, Kondo T, Tsujioka T, et al. Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis. Leukemia. 2010;24:748–55.

    Article  CAS  Google Scholar 

  17. Okamoto S, Tsujioka T, Suemori S, Kida J, Kondo T, Tohyama Y, et al. Withaferin A suppresses the growth of myelodysplasia and leukemia cell lines by inhibiting cell cycle progression. Cancer Sci. 2016;107:1302–14.

    Article  CAS  Google Scholar 

  18. Tsujioka T, Yokoi A, Itano Y, Takahashi K, Ouchida M, Okamoto S, et al. Five-aza-20-deoxycytidine-induced hypomethylation of cholesterol 25-hydroxylase gene is responsible for cell death of myelodysplasia/leukemia cells. Sci Rep. 2015;5:e16709.

    Article  Google Scholar 

  19. Yokoyama K, Kaji H, He J, Tanaka C, Hazama R, Kamigaki T, et al. Rab27a negatively regulates phagocytosis by prolongation of the actin-coating stage around phagosomes. J Biol Chem. 2011;286:5375–82.

    Article  CAS  Google Scholar 

  20. Liu J, Wang QC, Cui XS, Wang ZB, Kim NH, Sun SC. MKlp2 inhibitor paprotrain affects polar body extrusion during mouse oocyte maturation. Reprod Biol Endocrinol. 2013;11:117.

    Article  Google Scholar 

  21. Labrière C, Talapatra SK, Thoret S, Bougeret C, Kozielski F, Guillou C. New MKLP-2 inhibitors in the paprotrain series: design, synthesis and biological evaluations. Bioorg Med Chem. 2016;24:721–34.

    Article  Google Scholar 

  22. UCSC Genome Browser. http://genome.ucsc.edu/cgi-bin/hgGene?hgsid=603509401_N8DVtcq4MYasazFcItiOB6nzGPt0&hgg_section_microarray_close=0#microarray. Accessed 20 Apr 2018.

  23. Hao S, Chen C, Cheng T. Cell cycle regulation of hematopoietic stem or progenitor cells. Int J Hematol. 2016;103:487–97.

    Article  CAS  Google Scholar 

  24. BloodSpot. a database of gene expression profiles and transcriptional programs for healthy and malignant haematopoiesis http://servers.binf.ku.dk/bloodspot/. Accessed 1 Aug 2018.

  25. Esendagli G, Canpinar H, Yilmaz G, Kaymaz FF, Kansu E, Guc D. Fibronectin promotes the phorbol 12-myristate 13-acetate-induced macrophage differentiation in myeloid leukemia cells. Int J Hematol. 2009;89:167–72.

    Article  CAS  Google Scholar 

  26. Hagiwara Y, Kasukabe T, Kaneko Y, Niitsu N, Okabe-Kado J. Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells. Int J Hematol. 2010;92:136–43.

    Article  CAS  Google Scholar 

  27. Khongkow P, Gomes AR, Gong C, Man EP, Tsang JW, Zhao F, et al. Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance. Oncogene. 2016;35:990–1002.

    Article  CAS  Google Scholar 

  28. Stangel D, Erkan M, Buchholz M, Gress T, Michalski C, Raulefs S, et al. Kif20a inhibition reduces migration and invasion of pancreatic cancer cells. J Surg Res. 2015;197:91–100.

    Article  CAS  Google Scholar 

  29. Asahara S, Takeda K, Yamao K, Maguchi H, Yamaue H. Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. J Transl Med. 2013;11:291.

    Article  Google Scholar 

  30. Suzuki N, Hazama S, Iguchi H, Uesugi K, Tanaka H, Hirakawa K, et al. Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study. Cancer Sci. 2017;108:73–80.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and in part by a Kawasaki Medical School project grant.

Author information

Authors and Affiliations

  1. Division of Biochemistry, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, 670-8524, Japan

    Hiroyuki Morita, Hiroyuki Tabata & Yumi Tohyama

  2. Department of Laboratory Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan

    Akihito Matsuoka, Jun-ichiro Kida & Kaoru Tohyama

Authors
  1. Hiroyuki Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihito Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun-ichiro Kida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroyuki Tabata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kaoru Tohyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yumi Tohyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kaoru Tohyama.

Ethics declarations

Conflict of interest

All authors have no conflict of interest to declare.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morita, H., Matsuoka, A., Kida, Ji. et al. KIF20A, highly expressed in immature hematopoietic cells, supports the growth of HL60 cell line. Int J Hematol 108, 607–614 (2018). https://doi.org/10.1007/s12185-018-2527-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-018-2527-y

Keywords

Search

Navigation