Skip to main content

Advertisement

SpringerLink
Log in

Depletion of STYK1 inhibits intrahepatic cholangiocarcinoma development both in vitro and in vivo

  • Original Article
  • Published:
Tumor Biology

Abstract

Intrahepatic cholangiocarcinoma (ICC) has been reported to be the second most common primary hepatic carcinoma worldwide, and very limited therapies are currently available. Serine threonine tyrosine kinase (STYK1), a member of the receptor tyrosine kinase family, exhibits tumorigenicity in many types of cancers and is a potential therapeutic target for ICC. In this study, STYK1 was knocked down in the ICC cell lines HCCC-9810 and RBE via a lentivirus-mediated system using short hairpin RNA (shRNA). Next, cell proliferation, colony formation, cell cycle progression, tumor formation in nude mice, migration and invasion, and the expression levels of cell cycle proteins in Lv-sh STYK1- or Lv-sh Con-infected cells were analyzed by CCK-8 assay, colony formation evaluation, flow cytometry, tumor formation evaluation, wound scratch assay, transwell assay, and western blotting. The results indicated that depletion of STYK1 inhibits ICC development both in vitro and in vivo.

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
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Suzuki H, Komuta M, Bolog A, Yokobori T, Wada S, Araki K, Kubo N, Watanabe A, Tsukagoshi M, Kuwano H. Relationship between 18-f-fluoro-deoxy-d-glucose uptake and expression of glucose transporter 1 and pyruvate kinase m2 in intrahepatic cholangiocarcinoma. Dig Liver Dis. 2015;47:590–6.

    Article  CAS  PubMed  Google Scholar 

  2. Hubbard SR, Till JH. Protein tyrosine kinase structure and function. Annu Rev Biochem. 2000;69:373–98.

    Article  CAS  PubMed  Google Scholar 

  3. Robinson DR, YM W, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene. 2000;19:5548–57.

    Article  CAS  PubMed  Google Scholar 

  4. Zwick E, Bange J, Ullrich A. Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer. 2001;8:161–73.

    Article  CAS  PubMed  Google Scholar 

  5. Chen P, Li WM, Lu Q, Wang J, Yan XL, Zhang ZP, Li XF. Clinicopathologic features and prognostic implications of NOK/STYK1 protein expression in non-small cell lung cancer. BMC Cancer. 2014;14:402.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Liu L, XZ Y, Li TS, Song LX, Chen PL, Suo TL, Li YH, Wang SD, Chen Y, Ren YM, Zhang SP, Chang ZJ, Fu XY. A novel protein tyrosine kinase NOK that shares homology with platelet- derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice. Cancer Res. 2004;64:3491–9.

    Article  CAS  PubMed  Google Scholar 

  7. Fambrough D, McClure K, Kazlauskas A, Lander ES. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell. 1999;97:727–41.

    Article  CAS  PubMed  Google Scholar 

  8. Chen Y, Li YH, Chen XP, Gong LM, Zhang SP, Chang ZJ, Zhang XF, XY F, Liu L. Point mutation at single tyrosine residue of novel oncogene NOK abrogates tumorigenesis in nude mice. Cancer Res. 2005;65:10838–46.

    Article  CAS  PubMed  Google Scholar 

  9. Li YH, Wang YY, Zhong S, Rong ZL, Ren YM, Li ZY, Zhang SP, Chang ZJ, Liu L. Transmembrane helix of novel oncogene with kinase-domain (NOK) influences its oligomerization and limits the activation of RAS/MPAK signaling. Mol Cell. 2009;27:39–45.

    Article  Google Scholar 

  10. Ding X, Jiang QB, Li R, Chen S, Zhang S. NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in endosomes. Biochem Biophys Res Commun. 2012;421:468–73.

    Article  CAS  PubMed  Google Scholar 

  11. Orang AV, Safaralizadeh R, Hosseinpour Feizi MA, Somi MH. Diagnostic relevance of overexpressed serine threonine tyrosine kinase/novel oncogene with kinase domain (STYK1/NOK) mRNA in colorectal cancer. Asian Pac J Cancer Prev. 2014;15:6685–9.

    Article  PubMed  Google Scholar 

  12. Amachika T, Kobayashi D, Moriai R, Tsuji N, Watanabe N. Diagnostic relevance of overexpressed mRNA of novel oncogene with kinase-domain (NOK) in lung cancers. Lung Cancer. 2007;56:337–40.

    Article  PubMed  Google Scholar 

  13. Kimbro KS, Duschene K, Willard M, Moore JA, Freeman S. A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Mol Biol Rep. 2008;35:23–7.

    Article  CAS  PubMed  Google Scholar 

  14. Jackson KA, Oprea G, Handy J, Kimbro KS. Aberrant STYK1 expression in ovarian cancer tissues and cell lines. J Ovarian Res. 2009;2:15.

    Article  PubMed  PubMed Central  Google Scholar 

  15. BL Y, Peng XH, Zhao FP, Liu X, Lu J, Wang L, Li G, Chen HH, Li XP. MicroRNA-378 functions as an onco-miR in nasopharyngeal carcinoma by repressing TOB2 expression. Int J Oncol. 2014;44:1215–22.

    Google Scholar 

  16. Lee MM, Chen YY, Liu PY, Hsu S, Sheu MJ. Pipoxolan inhibits CL1-5 lung cancer cells migration and invasion through inhibition of MMP-9 and MMP-2. Chem Biol Interact. 2015;236:19–30.

    Article  CAS  PubMed  Google Scholar 

  17. Wang Z, Tang X, Zhang Y, Qi R, Li Z, Zhang K, Liu Z, Yang X. Lobaplatin induces apoptosis and arrests cell cycle progression in human cholangiocarcinoma cell line RBE. Biomedicine Pharmacother. 2012;66:161–6.

    Article  CAS  Google Scholar 

  18. Shi RY, Yang XR, Shen QJ, Yang LX, Xu Y, Qiu SJ, Sun YF, Zhang X, Wang Z, Zhu K, Qin WX, Tang ZY, Fan J, Zhou J. High expression of Dickkopf-related protein 1 is related to lymphatic metastasis and indicates poor prognosis in intrahepatic cholangiocarcinoma patients after surgery. Cancer. 2013;119:993–1003.

    Article  CAS  PubMed  Google Scholar 

  19. Eriksson JE, Dechat T, Grin B, Helfand B, Mendez M, Pallari HM, Goldman RD. Introducing intermediate filaments: from discovery to disease. J Clin Invest. 2009;119:1763–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cabeen MT, Jacobs-Wagner C. The bacterial cytoskeleton. Annu Rev Genet. 2010;44:365–92.

    Article  CAS  PubMed  Google Scholar 

  21. Goldman RD, Khuon S, Chou YH, Opal P, Steinert PM. The function of intermediate filaments in cell shape and cytoskeletal integrity. J Cell Biol. 1996;134:971–83.

    Article  CAS  PubMed  Google Scholar 

  22. Leader M, Collins M, Patel J, Henry K. Vimentin: an evaluation of its role as a tumour marker. Histopathology. 1987;11:63–72.

    Article  CAS  PubMed  Google Scholar 

  23. Ramis-Conde I, Chaplain MA, Anderson AR, Drasdo D. Multi-scale modelling of cancer cell intravasation: the role of cadherins in metastasis. Phys Biol. 2009;6:016008.

    Article  PubMed  Google Scholar 

  24. Yuan J, Yan R, Kramer A, Eckerdt F, Roller M, Kaufmann M, Strebhardt K. Cyclin b1 depletion inhibits proliferation and induces apoptosis in human tumor cells. Oncogene. 2004;23:5843–52.

    Article  CAS  PubMed  Google Scholar 

  25. Zhang F, Liu B, Wang Z, XJ Y, Ni QX, Yang WT, Mukaida N, Li YY. A novel regulatory mechanism of Pim-3 kinase stability and its involvement in pancreatic cancer progression. Mol Cancer Res. 2013;11:1508–20.

    Article  CAS  PubMed  Google Scholar 

  26. Lee MG, Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987;327:31–5.

    Article  CAS  PubMed  Google Scholar 

  27. Kristjansdottir K, Rudolph J. Cdc25 phosphatases and cancer. Chem Biol. 2004;11:1043–51.

    Article  CAS  PubMed  Google Scholar 

  28. Canel M, Serrels A, Frame MC, Brunton VG. E-cadherin-integrin crosstalk in cancer invasion and metastasis. J Cell Sci. 2013;126:393–401.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the International Science and Technology Cooperation Program of China (No. 2014DFA31420) and the National Natural Science Foundation of China (No. 81160311).

Author information

Authors and Affiliations

  1. Department of Biliary-Hepatic Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, 550001, China

    Mei-yuan Chen, Hao Zhang, Jian-xin Jiang, Cheng-yi Sun, Chao Yu & She Tian

Authors
  1. Mei-yuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian-xin Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng-yi Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. She Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jian-xin Jiang or Cheng-yi Sun.

Ethics declarations

All animal experiments were approved by the Animal Care Committee of the Affiliated Hospital of Guiyang Medical College.

Additional information

Mei-yuan Chen and Hao Zhang equally contribute to this study as the co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, My., Zhang, H., Jiang, Jx. et al. Depletion of STYK1 inhibits intrahepatic cholangiocarcinoma development both in vitro and in vivo. Tumor Biol. 37, 14173–14181 (2016). https://doi.org/10.1007/s13277-016-5188-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5188-6

Keywords

Search

Navigation