Crosstalk of FGFR1 signaling and choline metabolism promotes cell proliferation and survival in prostate cancer cells,International Journal of Cancer

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Crosstalk of FGFR1 signaling and choline metabolism promotes cell proliferation and survival in prostate cancer cells
International Journal of Cancer ( IF 5.7 ) Pub Date : 2022-01-05 , DOI: 10.1002/ijc.33922
Zhichao Fan ₁ , Jisheng Ma ₁ , Xuebo Pan ₁ , Liangcai Zhao ₁ , Yuying Wu ₁ , Hui Lin ₁ , Yidan Zhao ₁ , Haowei Jiang ₁ , Tingting Pan ₁ , Xiaokun Li ₁ , Fen Wang ₂ , Cong Wang ₁

Affiliation

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.

中文翻译：

FGFR1信号和胆碱代谢的串扰促进前列腺癌细胞的细胞增殖和存活

异位 I 型成纤维细胞生长因子受体 (FGFR1) 的获得是前列腺癌 (PCa) 的共同特征，前列腺癌是男性最常见的诊断癌症。然而，异位 FGFR1 如何促进 PCa 进展尚不清楚。在我们的研究中，我们发现 DU145 人 PCa 细胞中FGFR1的消融改变了细胞代谢物谱。在这些变化中，胆碱代谢曲线因FGFR1消融而发生的变化最为显着。详细的表征揭示了FGFR1的消融多种胆碱代谢酶的表达改变。在 FGFR1 调节的胆碱代谢酶的变化中，胆碱激酶 α (CHKA) 的下调是最显着的变化，它将游离胆碱磷酸化为磷酸胆碱。FGFR1的消融减弱了胆碱促进细胞增殖和存活的活性。此外，CHKA的消耗DU145 细胞中的 FGF 信号传导活性受损。我们还首次证明 FGFR1 与 CHKA 形成复合物，表明 FGFR1 在翻译后水平调节 CHKA。与之前关于异位 FGFR1 有助于 PCa 进展和转移的报告一起，我们的研究结果揭示了一种新机制，即 FGFR1 通过失调胆碱代谢促进 PCa 进展，并且 FGFR1-胆碱代谢之间的串扰可能是管理 PCa 的潜在目标进展。

更新日期：2022-01-05

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