Crosstalk of FGFR1 signaling and choline metabolism promotes cell proliferation and survival in prostate cancer cells. Issue 9 (18th January 2022)

• Record Type: Journal Article
• Authors: Fan, Zhichao; Ma, Jisheng; Pan, Xuebo; Zhao, Liangcai; Wu, Yuying; Lin, Hui; Zhao, Yidan; Jiang, Haowei; Pan, Tingting; Li, Xiaokun; Wang, Fen; Wang, Cong
• Is Part Of: International journal of cancer. Volume 150:Issue 9(2022)
• Page Start: 1525
• Page End: 1536
• Publication Date: 2022-01-18
• Subjects: choline kinase -- FGFR1 -- NMR -- prostate cancer; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33922
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Ectopic FGFR1 expression is a common feature of prostate cancer and malignant transformation of prostate epithelial cells, which has been associated with increased levels of choline derivatives. Whether and how ectopic FGFR1 contributes to dysregulated choline metabolism remains unclear, however. Our study demonstrates that FGFR1 alters the expression of multiple choline metabolism enzymes. FGFR1 not only forms complexes with choline kinase α (CHKα) but also regulates CHKα at the posttranslational level. Furthermore, CHKα depletion compromises FGF signaling activity in human prostate cancer cells, highlighting the crosstalk between FGFR1 and choline metabolism as a potential target for controlling prostate cancer progression.