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

Tumour Biol. 2016 Aug;37(8):10587-93. doi: 10.1007/s13277-016-4954-9. Epub 2016 Feb 9.

Abstract

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.

Keywords: AKT; Chemotherapy; PI3K; Sphingosine kinase 1; Sphingosine-1-phosphate; Triple-negative breast cancer.

Publication types

  • Retracted Publication

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Apoptosis
  • Cell Division
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Lysophospholipids / metabolism
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Phosphatidylinositol 3-Kinases / physiology*
  • Proto-Oncogene Proteins c-akt / physiology*
  • RNA / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction*
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Stem Cell Assay

Substances

  • Adaptor Proteins, Signal Transducing
  • Lysophospholipids
  • Neoplasm Proteins
  • RNA, Small Interfering
  • RNA, recombinant
  • SPHKAP protein, human
  • sphingosine 1-phosphate
  • RNA
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Sphingosine