2. Academic Validation
  3. FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells

FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells

  • Commun Biol. 2024 Aug 17;7(1):1011. doi: 10.1038/s42003-024-06704-6.
Hui Lin # 1,  Shuaijun Lin # 1,  Liuhong Shi # 2,  Guangsen Xu 1,  Manjie Lin 1,  Supeng Li 1,  Jiale Chen 1,  Zhiquan Li 1,  Catherine Nakazibwe 1,  Yunbei Xiao 3,  Xiaokun Li 4,  Xuebo Pan 5,  Cong Wang 6
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of Head and Neck Surgery, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 3 Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 4 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. xiaokunli@wmu.edu.cn.
  • 5 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. xuebopan@wmu.edu.cn.
  • 6 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. cwang@wmu.edu.cn.
  • # Contributed equally.
PMID: 39154074 DOI: 10.1038/s42003-024-06704-6
Abstract

The acquisition of ectopic Fibroblast Growth Factor receptor 1 (FGFR1) expression is well documented in prostate Cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes Transferrin Receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the Anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

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