Tumor Biology

, Volume 37, Issue 8, pp 10587–10593 | Cite as

RETRACTED ARTICLE: Overexpression of SphK1 enhances cell proliferation and invasion in triple-negative breast cancer via the PI3K/AKT signaling pathway

  • Jun Li
  • Zhangjun Song
  • Yiyu Wang
  • Yue Yin
  • Ying Liu
  • Rong Yuan
  • Xing Nan
Original Article


Sphingosine kinase 1 (SphK1) expression is elevated in various cancers and is associated with shorter survival times for patients. However, the molecular mechanism of SphK1 up-regulation in triple-negative breast cancer (TNBC) remains unclear. In this study, we assayed the expression level of SphK1 in TNBC tissues by qRT-PCR and immunohistochemistry. The level of S1P was quantified by ELISA in the serum of TNBC patients. Our results found that the levels of SphK1 and S1P were significantly increased in TNBC patients compared with normal control. Furthermore, knockdown of SphK1 with siRNA decreased TNBC cell proliferation and inhibited cell migration/invasion. These data suggest that SphK1 has an important role in TNBC and presents an attractive therapeutic target for the treatment for TNBC.


Sphingosine kinase 1 Sphingosine-1-phosphate Triple-negative breast cancer Chemotherapy AKT PI3K 


Compliance with ethical standards

Our study was permitted by Center’s Ethnics Committee of Shaanxi Provincial Tumor Hospital, and informed consent was obtained from all patients.

Conflicts of interest



  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, et al. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res. 2007;9(1):R4.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23(29):7350–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Tomao F, Papa A, Zaccarelli E, Rossi L, Caruso D, Minozzi M, et al. Triple-negative breast cancer: new perspectives for targeted therapies. Onco Targets Ther. 2015;8:177–93.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C, et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer. 2009;9(1):29–33.CrossRefPubMedGoogle Scholar
  7. 7.
    Hait NC, Oskeritzian CA, Paugh SW, Milstien S, Spiegel S. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006;1758:2016–26.CrossRefPubMedGoogle Scholar
  8. 8.
    Pyne NJ, Tonelli F, Lim KG, Long JS, Edwards J, Pyne S. Sphingosine 1-phosphate signalling in cancer. Biochem Soc Trans. 2012;40(1):94–100.CrossRefPubMedGoogle Scholar
  9. 9.
    Liu SQ, Huang JA, Qin MB, Su YJ, Lai MY, Jiang HX, et al. Sphingosine kinase 1 enhances colon cancer cell proliferation and invasion by upregulating the production of MMP-2/9 and uPA via MAPK pathways. Int J Colorectal Dis. 2012;27(12):1569–78.CrossRefPubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Liu Y, Baglia M, Zheng Y, Blot W, Bao PP, Cai H, et al. ALDH1A1 mRNA expression in association with prognosis of triple-negative breast cancer. Oncotarget. 2015;6(38):41360–9.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Bansal N, Petrie K, Christova R, Chung CY, Leibovitch BA, Howell L, et al. Targeting the SIN3A-PF1 interaction inhibits epithelial to mesenchymal transition and maintenance of a stem cell phenotype in triple negative breast cancer. Oncotarget. 2015;6(33):34087–105.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Kim HS, Yoon G, Ryu JY, Cho YJ, Choi JJ, Lee YY, et al. Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer. Oncotarget. 2015;6(29):26746–56.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chen MH, Yen CC, Cheng CT, Wu RC, Huang SC, Yu CS, et al. Identification of SPHK1 as a therapeutic target and marker of poor prognosis in cholangiocarcinoma. Oncotarget. 2015;6(27):23594–608.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Tsukamoto S, Huang Y, Kumazoe M, Lesnick C, Yamada S, Ueda N, et al. Sphingosine kinase-1 protects multiple myeloma from apoptosis driven by cancer-specific inhibition of RTKs. Mol Cancer Ther. 2015;14(10):2303–12.CrossRefPubMedGoogle Scholar
  16. 16.
    Yang L, Weng W, Sun ZX, Fu XJ, Ma J, Zhuang WF. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo. Biochem Biophys Res Commun. 2015;460(4):903–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Malavaud B, Pchejetski D, Mazerolles C, de Paiva GR, Calvet C, Doumerc N, et al. Sphingosine kinase-1 activity and expression in human prostate cancer resection specimens. Eur J Cancer. 2010;46(18):3417–24.CrossRefPubMedGoogle Scholar
  18. 18.
    Tan SS, Khin LW, Wong L, Yan B, Ong CW, Datta A, et al. Sphingosine kinase 1 promotes malignant progression in colon cancer and independently predicts survival of patients with colon cancer by competing risk approach in South Asian population. Clin Transl Gastroenterol. 2014;5, e51.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    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.PubMedGoogle Scholar
  20. 20.
    Xu Y, Dong B, Huang J, Kong W, Xue W, Zhu Y, et al. Sphingosine kinase 1 is overexpressed and promotes adrenocortical carcinoma progression. Oncotarget. 2015. doi: 10.18632/oncotarget.6564.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jun Li
    • 1
  • Zhangjun Song
    • 2
  • Yiyu Wang
    • 1
  • Yue Yin
    • 1
  • Ying Liu
    • 1
  • Rong Yuan
    • 1
  • Xing Nan
    • 1
  1. 1.Tumor Research CenterShaanxi Provincial Tumor HospitalXi’anChina
  2. 2.Breast Surgery CenterShaanxi Provincial Tumor HospitalXi’anChina

Personalised recommendations