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GOLPH3 promotes glioma progression via facilitating JAK2-STAT3 pathway activation

Shishuang Wu1, Jiale Fu1, Yu Dong1

  • 1The Graduate School, Xuzhou Medical University, Xuzhou, 221002, Jiangsu, People's Republic of China.

Journal of Neuro-Oncology
|May 2, 2018
PubMed
Abstract

Insights

Golgi phosphoprotein 3 (GOLPH3) promotes glioma by scaffolding Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) interactions, enhancing their activation and driving cell proliferation.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Golgi phosphoprotein 3 (GOLPH3) is implicated in glioma progression by inhibiting EGFR endocytosis.
  • EGFR signaling pathways, including JAK2-STAT3, are crucial in cancer development.
  • The precise mechanism by which GOLPH3 influences JAK2-STAT3 signaling in glioma remains to be elucidated.

Purpose of the Study:

  • To investigate the regulatory role of GOLPH3 in the JAK2-STAT3 signaling pathway.
  • To explore the mechanism by which GOLPH3 influences glioma cell proliferation via JAK2-STAT3 signaling.

Main Methods:

  • Western blotting, immunohistochemistry, and tissue microarrays were used to assess protein expression in glioma tissues.
  • Lentivirus-mediated gene manipulation was employed to alter GOLPH3 levels in U251 and U87 glioma cell lines.
  • Co-immunoprecipitation assays were performed to analyze protein-protein interactions, and cell proliferation was quantified using CCK8 and EdU assays.

Main Results:

  • GOLPH3, JAK2, and STAT3 were significantly upregulated and correlated in human glioma tissues.
  • GOLPH3 modulated the activation of JAK2 and STAT3, influencing the expression of STAT3 target genes cyclin D1 and c-myc.
  • GOLPH3 physically interacted with JAK2 and STAT3, affecting their complex formation and subsequent activation, which drove cell proliferation.

Conclusions:

  • GOLPH3 functions as a scaffold protein, facilitating the interaction and activation of JAK2 and STAT3.
  • This GOLPH3-mediated regulation of JAK2-STAT3 signaling is a key mechanism driving glioma cell proliferation.
  • Targeting GOLPH3 may offer a therapeutic strategy for glioma by disrupting crucial signaling pathways.
Keywords:
GOLPH3GliomaJAK2ProliferationSTAT3

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