Crosstalk of FGFR1 signaling and choline metabolism promotes cell proliferation and survival in prostate cancer cells

Zhichao Fan, Jisheng Ma, Xuebo Pan, Liangcai Zhao, Yuying Wu, Hui Lin, Yidan Zhao, Haowei Jiang, Tingting Pan, Xiaokun Li, Fen Wang, Cong Wang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The acquisition of ectopic type I fibroblast growth factor receptor (FGFR1) is a common feature of prostate cancer (PCa), the most frequently diagnostic cancer in men. However, how ectopic FGFR1 contributes to PCa progression is not well understood. In our study we showed that ablation of FGFR1 in DU145 human PCa cells changed the cell metabolite profile. Among the changes, the choline metabolism profile was the most significantly altered by FGFR1 ablation. Detailed characterization revealed that ablation of FGFR1 altered expression of multiple choline metabolism enzymes. Among the changes of FGFR1-regulated choline metabolic enzymes, downregulation of choline kinase α (CHKA) is the most prominent changes, which phosphorylates free choline to phosphocholine. Ablation of FGFR1 blunted the activity of choline to promote cell proliferation and survival. Furthermore, depletion of CHKA compromised FGF signaling activity in DU145 cells. We also first time demonstrated that FGFR1 formed complex with CHKA, suggesting that FGFR1 regulated CHKA at the posttranslational level. Together with the previous report that ectopic FGFR1 contributes to PCa progression and metastasis, our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by dysregulating choline metabolism, and that the crosstalk between FGFR1-choline metabolism can be a potential target for managing PCa progression.

Original languageEnglish (US)
Pages (from-to)1525-1536
Number of pages12
JournalInternational Journal of Cancer
Volume150
Issue number9
DOIs
StatePublished - May 1 2022

Keywords

  • FGFR1
  • NMR
  • choline kinase
  • prostate cancer
  • Cell Proliferation
  • Signal Transduction
  • Humans
  • Male
  • Receptor, Fibroblast Growth Factor, Type 1/genetics
  • Choline/metabolism
  • Prostate/pathology
  • Cell Line, Tumor
  • Prostatic Neoplasms/metabolism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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