Transcriptional upregulation of microtubule-associated protein 2 is involved in the protein kinase A-induced decrease in the invasiveness of glioma cells.

Abstract

BACKGROUND:

Malignant glioma is the most lethal primary tumor of the central nervous system, with notable cell invasion causing significant recurrence. Suppression of glioma invasion is very important for improving clinical outcomes. Drugs that directly disrupt the cytoskeleton have been developed for this purpose; however, drug resistance and unsatisfactory selectivity have limited their clinical use. Previously, we reported that protein kinase A (PKA, also known as cyclic-AMP dependent protein kinase) activation induced the differentiation of glioma cells.

METHODS:

We used several small molecular inhibitors and RNA interference, combined with wound healing assays, Matrigel transwell assay, and microscopic observation, to determine whether activation of the PKA pathway could inhibit the invasion of human glioma cells.

RESULTS:

Activation of PKA decreased the invasion of glioma cells. The mechanism operated via transcriptional upregulation of microtubule-associated protein 2 (MAP2), which was activated by the PKA pathway and led to ossification of microtubule dynamics via polymerization of tubulin. This resulted in morphological changes and a reduction in glioma cell invasion. Furthermore, chromosome immunoprecipitation and quantitative real-time polymerase chain reaction showed that signal transducer and activator of transcription 3 (STAT3) is involved in the transcriptional upregulation of MAP2.

CONCLUSION:

Our findings suggested that PKA may represent a potential target for anti-invasion glioma therapy and that the downstream modulators (eg, STAT3/MAP2) partially mediate the effects of PKA.

• Authors: Yuxi Zhou, Sihan Wu, Chaofeng Liang, Yuan Lin, Yan Zou, Kai Li, Bingzheng Lu, Minfeng Shu, Yijun Huang, Wenbo Zhu, Zhuang Kang, Dong Xu, Jun Hu, Guangmei Yan
• Journal: Neuro-oncology (Neuro Oncol) Vol. 17 Issue 12 Pg. 1578-88 (Dec 2015) ISSN: 1523-5866 [Electronic] England
• PMID: 26014048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• MAP2 protein, human
• Microtubule-Associated Proteins
• Cyclic AMP-Dependent Protein Kinases

Topics

• Animals
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Glioma (metabolism, pathology)
• Humans
• Microtubule-Associated Proteins (metabolism)
• Neoplasm Invasiveness
• Rats
• Signal Transduction
• Transcription, Genetic
• Up-Regulation