Osteopontin induces beta-catenin signaling through activation of Akt in prostate cancer cells.

Abstract

Secretion of osteopontin (OPN) by cancer cells is a known mediator of tumorigenesis and cancer progression in both experimental and clinical studies. Our work demonstrates that OPN can activate Akt, an important step in cancer progression. Both ILK and PI3K are integral proteins in the OPN/Akt pathway, as inhibition of either kinase leads to a loss of OPN-mediated Akt activation. Subsequent to OPN-induced Akt activation, we observe inactivation of GSK-3beta, a regulator of beta-catenin. Osteopontin stimulation leads to an overall increase in beta-catenin protein levels with a resultant transfer of beta-catenin to the nucleus. Through the nuclear import of beta-catenin, OPN increases both the transcription and protein levels of MMP-7 and CD44, which are known TCF/LEF transcription targets. This work describes an important aspect of cancer progression induced by OPN.

• Authors: Brian W Robertson, Meenakshi A Chellaiah
• Journal: Experimental cell research (Exp Cell Res) Vol. 316 Issue 1 Pg. 1-11 (Jan 01 2010) ISSN: 1090-2422 [Electronic] United States
• PMID: 19850036 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CD44 protein, human
• Enzyme Inhibitors
• Hyaluronan Receptors
• Phosphatidylinositol Phosphates
• Phosphoinositide-3 Kinase Inhibitors
• TCF Transcription Factors
• beta Catenin
• phosphatidylinositol 3-phosphate
• Osteopontin
• integrin-linked kinase
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• MMP7 protein, human
• Matrix Metalloproteinase 7

Topics

• Active Transport, Cell Nucleus (genetics)
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic (physiology)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Hyaluronan Receptors (metabolism)
• Male
• Matrix Metalloproteinase 7 (metabolism)
• Models, Biological
• Osteopontin (pharmacology, physiology)
• Phosphatidylinositol Phosphates (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation (drug effects)
• Prostatic Neoplasms (metabolism)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects, physiology)
• TCF Transcription Factors (metabolism)
• Transfection
• beta Catenin (metabolism)