ATX–LPA Axis Induces Expression of OPN in Hepatic Cancer Cell SMMC7721

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. Anat Rec, 294:406-411, 2011. V V C 2010 Wiley-Liss, Inc.

Proteomics Based Identification of Autotaxin As An Anti-Hepatitis B Virus Factor and a Promoter of Hepatoma Cell Invasion and Migration

“…Belloni’s group further confirmed that IFN could inhibit HBV replication by decreasing the transcription of pgRNA from the HBV cccDNA minichromosome [38]. Since LPA can act on distinct G protein-coupled receptors, it plays an important role in activating multiple signaling cascades [39], including, but not exclusively, the PI3K/Akt signaling pathway [40]. When inhibitors of LPA were added, phosphorylation of the PI3K/Akt pathway was reduced [40], affecting in turn the phosphorylation of STAT1 [41] and the activation of gene expression.…”

“…Since LPA can act on distinct G protein-coupled receptors, it plays an important role in activating multiple signaling cascades [39], including, but not exclusively, the PI3K/Akt signaling pathway [40]. When inhibitors of LPA were added, phosphorylation of the PI3K/Akt pathway was reduced [40], affecting in turn the phosphorylation of STAT1 [41] and the activation of gene expression. Additionally, IFN-activated JAK-STAT pathways were completed by activating the PI3K/Akt pathway [42] through allowing translation of IFN-stimulated genes, such as ISG15 [42], and IFN β1 [43].…”

Reversal Effect of Melanoma Differentiation Associated Gene‐7/Interleukin‐24 on Multidrug Resistance in Human Hepatocellular Carcinoma Cells

“…It is also one of the most common cancers in China. HCC is one of the most crucial public health burdens worldwide and is associated with several risk factors such as genetic factors, lifestyle choices, and environmental conditions (Zhang et al, 2011b). Chemotherapy is one of the major methods of treating HCC, but chemotherapeutic drug resistance is a major problem in cancer chemotherapy.…”

Osteopontin (OPN) Is an Important Protein to Mediate Improvements in the Biocompatibility of C Ion-Implanted Silicone Rubber

“…It is secreted from cells, works as both an ECM component and a soluble cytokine [25], and is able to bind to both RGD-containing integrins (αvβ1, αvβ3, αvβ5, αvβ1, α8β1) or non-RGD integrins (α4β1, α9β1) to promote cell survival, proliferation, migration, invasion, and metastasis [26]. Western blot results in Figure 4A showed that dermal fibroblasts cultured on C-SRs had higher OPN expression and secretion than those cultured on SR. Immuno-fluorescence images in Figure 4B further confirmed higher intracellular OPN expression in those dermal fibroblasts.…”