ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF-κB signaling pathway

IUBMB Life. 2014 Apr;66(4):300-8. doi: 10.1002/iub.1268. Epub 2014 Apr 23.

Abstract

Metastasis of tumor cells is the most deadly attribute of breast cancer patients. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. The objective of this study is to clarify the possible role and mechanism of ST6GalNAcII in the metastasis process of breast carcinoma. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAc II in breast carcinoma cell lines and tissue specimens. PI3K/AKt signaling pathway was also analyzed. The high expression level of ST6GalNAcII was corresponding to invasive phenotype of breast cancer cells both in vitro and in vivo. Further data indicated that manipulation of ST6GalNAcII gene expression led to alter the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Blocking the PI3K/Akt pathway resulted in reduced capacity in invasion of MDA-MB-231 cells. ST6GalNAcII elucidated the unusual properties of invasion in breast cancer cell via modulating the PI3K/AKt signaling pathway.

Keywords: PI3K/AKt signaling; ST6GalNAcII; breast carcinoma; metastasis.

MeSH terms

  • Animals
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Nude
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialyltransferases / antagonists & inhibitors
  • Sialyltransferases / genetics
  • Sialyltransferases / metabolism*
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • Sialyltransferases
  • galactosyl-1-3-N-acetylgalactosaminyl-specific 2,6-sialyltransferase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt