Integrative transcriptome and proteome study to identify the signaling network regulated by POPX2 phosphatase.

Abstract

POPX2 is a serine/threonine phosphatase belonging to the protein phosphatase 2C (PP2C) family that has been found to be elevated in invasive breast cancer cells. Silencing of POPX2 results in lower cell motility and invasiveness. The molecular mechanism of POPX2-regulated cell motility is not well understood. To identify the relevant signaling pathways, we investigated the transcriptome and proteome of POPX2-knockdown MDA-MB-231 breast cancer cells. Our data suggest that POPX2 might be involved in the regulation of focal adhesions and cytoskeleton dynamics through the regulation of MAP kinase (MAPK1/3) and glycogen synthase kinase 3 (GSK3α/β) activities. Silencing POPX2 alters phosphorylation levels of MAPK1/3 and GSK3α/β and results in reduced activity of these kinases. Both MAPK and GSK3 are known to regulate the activities of transcription factors. MAPK1/3 are also implicated in the phosphorylation of stathmin. The level of phospho-stathmin was found to be lower in POPX2 knockdown cells. As phosphorylation of stathmin inhibits its microtubule severing activity, we observed less stable microtubules in POPX2 knockdown cells. Taken together, our data suggest that POPX2 might regulate cell motility through its regulation of the MAPK1/3, leading to changes in the cytoskeleton and cell motility.

• Authors: Songjing Zhang, Tiannan Guo, Hei Chan, Siu Kwan Sze, Cheng-Gee Koh
• Journal: Journal of proteome research (J Proteome Res) Vol. 12 Issue 6 Pg. 2525-36 (Jun 07 2013) ISSN: 1535-3907 [Electronic] United States
• PMID: 23621870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Proteome
• STMN1 protein, human
• Stathmin
• Glycogen Synthase Kinase 3 beta
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Glycogen Synthase Kinase 3
• PPM1F protein, human
• Phosphoprotein Phosphatases

Topics

• Cell Line, Tumor
• Cell Movement
• Cytoskeleton (genetics, metabolism)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Glycogen Synthase Kinase 3 (genetics, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Isoenzymes (genetics, metabolism)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Phosphoprotein Phosphatases (deficiency, genetics)
• Phosphorylation
• Proteome (genetics, metabolism)
• Signal Transduction (genetics)
• Stathmin (genetics, metabolism)
• Transcriptome