ATX-LPA axis induces expression of OPN in hepatic cancer cell SMMC7721

Anat Rec (Hoboken). 2011 Mar;294(3):406-11. doi: 10.1002/ar.21324. Epub 2010 Dec 31.

Abstract

Osteopontin (OPN) and autotaxin (ATX) are important chemokines involved in the survival, proliferation, migration, invasion, and metastasis of many cancer cells. The focus of the study was to investigate the relationship between OPN and ATX-lysophosphatidic acid (LPA) axis. The expression of OPN and its cellular cascades were determined by western blot and real-time quantitative transcription polymerase chain reaction (real-time PCR) analyses. Cell migration activity was determined by a Transwell-migration assay. In comparison with nontreated cells, we found that the ATX-LPA axis upregulated OPN expression by 2.91-fold in protein levels and 2.52-fold in mRNA levels. The ATX-LPA axis activates Akt and ATX/LPC-induced OPN expression in SMMC7721 cells was largely reduced by the inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt or LPA receptor. This study provides the first evidence that the induction of the OPN expression by ATX-LPA axis was mediated by the activation of Akt through LPA receptors and OPN was required for migration of SMMC7721 cells induced by ATX-LPA axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Movement
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Lysophospholipids / metabolism*
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Osteopontin / antagonists & inhibitors
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphodiesterase I / genetics
  • Phosphodiesterase I / metabolism*
  • Phosphoric Diester Hydrolases
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Lysophospholipids
  • Multienzyme Complexes
  • RNA, Messenger
  • RNA, Small Interfering
  • Osteopontin
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • alkylglycerophosphoethanolamine phosphodiesterase
  • Pyrophosphatases
  • lysophosphatidic acid