Skip to main content

Advertisement

SpringerLink
Log in

SphK1 promotes tumor cell migration and invasion in colorectal cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Sphingosine kinase 1 (SphK1), which phosphorylates sphingosine to sphingosine-1-phosphate (S1P), is overexpressed in various types of cancers and may act as an oncogene in tumorigenesis. However, little is known about the role of SphK1 in CRC patients. We studied the expression of SphK1 in 85 cases of CRC tissues by immunohistochemistry, qRT-PCR, and western blot. We also evaluated the effect of SphK1 on cell proliferation and invasion by MTT and transwell invasion assay. SphK1 is overexpressed in CRC tissues and cell lines, and upregulation of SphK1 correlated significantly with the following parameters: lymph node metastasis, liver metastasis, and advanced TNM stage. SphK1 knockdown results in inhibition of cancer cell proliferation. Inhibition of CRC cell migration and invasion is also evident through reversal of EMT by increases in E-cadherin expression and decreases in vimentin expression. In conclusion, SphK1 is associated with the proliferation and invasiveness of CRC cells and the SphK1 gene may contribute to a novel therapeutic approach against CRC.

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

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  2. Kobayashi H, Mochizuki H, Sugihara K, Morita T, Kotake K, Teramoto T, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 2007;141:67–75.

    Article  PubMed  Google Scholar 

  3. Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on colorectal cancer. Gastroenterology. 2012;143:844–57.

    Article  PubMed  Google Scholar 

  4. Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2014;259(4):735–43.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Shimada H, Tanaka K, Endou I, Ichikawa Y. Treatment for colorectal liver metastases: a review. Langenbecks Arch Surg. 2009;394:973–83.

    Article  PubMed  Google Scholar 

  6. Zhang H, Wang Q, Zhao Q, Di W. MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1. J Ovarian Res. 2013;6(1):84.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Yang YL, Ji C, Cheng L, He L, Lu CC, Wang R, et al. Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells. Cancer Sci. 2012;103(8):1538–45.

    Article  CAS  PubMed  Google Scholar 

  8. Santulli P, Marcellin L, Noël JC, Borghese B, Fayt I, Vaiman D, et al. Sphingosine pathway deregulation in endometriotic tissues. Fertil Steril. 2012;97(4):904–11.

    Article  CAS  PubMed  Google Scholar 

  9. Datta A, Loo SY, Huang B, Wong L, Tan SS, Tan TZ, et al. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer. Oncotarget. 2014;5(15):5920–33.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang Y, Tang Q, Li M, Jiang S, Wang X. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun. 2014;444:199–204.

    Article  CAS  PubMed  Google Scholar 

  11. Van Cutsem E, Nordlinger B, Adam R, K€ohne CH, Pozzo C, Poston G. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006;42:2212–21.

    Article  PubMed  Google Scholar 

  12. Meng XD, Zhou ZS, Qiu JH, Shen WH, Wu Q, Xiao J. Increased SPHK1 expression is associated with poor prognosis in bladder cancer. Tumour Biol. 2014;35(3):2075–80.

    Article  CAS  PubMed  Google Scholar 

  13. Lu Z, Zhang W, Gao S, Jiang Q, Xiao Z, Ye L, et al. MiR-506 suppresses liver cancer angiogenesis through targeting sphingosine kinase 1 (SPHK1) mRNA. Biochem Biophys Res Commun. 2015;468(1–2):8–13.

    Article  CAS  PubMed  Google Scholar 

  14. Shi J, He YY, Sun JX, Guo WX, Li N, Xue J, et al. The impact of sphingosine kinase 1 on the prognosis of hepatocellular carcinoma patients with portal vein tumor thrombus. Ann Hepatol. 2015;14(2):198–206.

    PubMed  Google Scholar 

  15. Lufrano M, Jacob A, Zhou M, Wang P. Sphingosine kinase-1 mediates endotoxemia-induced hyperinflammation in aged animals. Mol Med Rep. 2013;8(2):645–9.

    PubMed  PubMed Central  Google Scholar 

  16. Karimian G, Buist-Homan M, Schmidt M, Tietge UJ, de Boer JF, Klappe K, et al. Sphingosine kinase-1 inhibition protects primary rat hepatocytes against bile salt-induced apoptosis. Biochim Biophys Acta. 2013;1832(12):1922–9.

    Article  CAS  PubMed  Google Scholar 

  17. Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217:998–1003.

    Article  CAS  PubMed  Google Scholar 

  18. Liotta LA, Steeq PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–36.

    Article  CAS  PubMed  Google Scholar 

  19. Guillermet-Guibert J, Davenne L, Pchejetski D, Saint-Laurent N, Brizuela L, Guilbeau-Frugier C, et al. Targeting the sphingolipid metabolism to defeat pancreatic cancer cell resistance to the chemotherapeutic gemcitabine drug. Mol Cancer Ther. 2009;8(4):809–20.

    Article  CAS  PubMed  Google Scholar 

  20. Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, Klaßen C, et al. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nat Commun. 2015;6:7796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhu L, Wang Z, Lin Y, Chen Z, Liu H, Chen Y, et al. Sphingosine kinase 1 enhances the invasion and migration of non-small cell lung cancer cells via the AKT pathway. Oncol Rep. 2015;33(3):1257–63.

    CAS  PubMed  Google Scholar 

  22. Ader I, Gstalder C, Bouquerel P, Golzio M, Andrieu G, Zalvidea S, et al. Neutralizing S1P inhibits intratumoral hypoxia, induces vascular remodelling and sensitizes to chemotherapy in prostate cancer. Oncotarget. 2015;6(15):13803–21.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cho SY, Cho S, Park E, Kim B, Sohn EJ, Oh B, et al. Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells. Bioorg Med Chem Lett. 2014;24(11):2560–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work is supported by the Science and Technology Planning Project of Guangdong Province (2013B021800284)

Author information

Authors and Affiliations

  1. Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Jianting Long

  2. Department of Clinic Nutrition, the First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Guangzhou, 510080, China

    Ying Xie, Junmei Yin, Wei Lu & Shi Fang

Authors
  1. Jianting Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junmei Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shi Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shi Fang.

Ethics declarations

Conflicts of interest

None

Additional information

Long J and Xie Y are co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Long, J., Xie, Y., Yin, J. et al. SphK1 promotes tumor cell migration and invasion in colorectal cancer. Tumor Biol. 37, 6831–6836 (2016). https://doi.org/10.1007/s13277-015-4542-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4542-4

Keyword

Search

Navigation