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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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. Res ults. 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.

Original languageEnglish (US)
Pages (from-to)1578-1588
Number of pages11
JournalNeuro-oncology
Volume17
Issue number12
DOIs
StatePublished - Dec 2015
Externally publishedYes

Keywords

  • CAMP/PKA pathway
  • Invasion
  • Malignant glioma
  • MAP2
  • Microtubule

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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