SphK1 promotes development of non‑small cell lung cancer through activation of STAT3

Int J Mol Med. 2021 Jan;47(1):374-386. doi: 10.3892/ijmm.2020.4796. Epub 2020 Nov 23.


Sphingosine kinase1 (SphK1) is an oncogenic enzyme that regulates tumor cell apoptosis, proliferation and survival. SphK1 has been reported to promote the development of non‑small cell lung cancer (NSCLC), although the underlying mechanism remains to be determined. The aim of the present study was to examine the expression and function of SphK1 in NSCLC and to explore the underlying molecular mechanism. The results of the present study demonstrated that SphK1 expression was upregulated in NSCLC tissues and cell lines. Overexpression of SphK1 increased the proliferation and migration of NSCLC cells. Additionally, overexpression of SphK1 induced expression of antiapoptotic and migration‑associated genes, such as Bcl‑2, matrix metallopeptidase 2 and cyclin D1. Of note, signal transducer and activator of transcription 3 (STAT3) was also activated in the SphK1‑overexpressing cells. By treatment with a STAT3 inhibitor, it was demonstrated that the SphK1‑induced changes in expression of target genes, as well as the increase in proliferation and migration of NSCLC cells were mediated by STAT3. In conclusion, the effects of SphK1 overexpression on the development of NSCLC were demonstrated to be mediated by the activation of STAT3. These results suggested that inhibition of the SphK1‑STAT3 axis may be a potential strategy for the treatment of NSCLC.

Keywords: non-small cell lung cancer; SphK1; STAT3; cyclin D1; MMP2; Bcl-2; Bcl-xl.

MeSH terms

  • A549 Cells
  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • STAT3 Transcription Factor / metabolism*


  • Neoplasm Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase