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

doi:10.1038/s42003-024-06704-6

科研成果详情

题名	FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells
作者	Lin, Hui 1; Lin, Shuaijun1; Shi, Liuhong 2; Xu, Guangsen1; Lin, Manjie1; Li, Supeng1; Chen, Jiale1; Li, Zhiquan1; Nakazibwe, Catherine 1; Xiao, Yunbei3; Li, Xiaokun1; Pan, Xuebo1; Wang, Cong1
发表日期	2024-08-17
发表期刊	Communications Biology 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	ELEMENT-BINDING PROTEIN ; EXPRESSION ; PROLIFERATION ; METABOLISM ; MECHANISMS ; CYCLE
摘要	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. Aberrant FGFR influences the labile iron pool by impacting on iron homeostasis regulators and LIP and IRP2 display a reciprocal relationship in exacerbating prostate cancer progression.
资助项目	National Natural Science Foundation of China (82173013, 82372941, 81971894); Natural Science Foundation of Zhejiang Province of China (Z23H160024, LR20H310001, LWY20H300001, LY17H150003); Project of Wenzhou Science Technology Bureau (Y2023161, Y20210085)
出版者	NATURE PORTFOLIO
ISSN	2399-3642
EISSN	2399-3642
卷号	7 期号:1
DOI	10.1038/s42003-024-06704-6
页数	13
WOS类目	Biology ; Multidisciplinary Sciences
WOS研究方向	Life Sciences & Biomedicine - Other Topics ; Science & Technology - Other Topics
WOS记录号	WOS:001292875700005
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39154074
SCOPUSEID	2-s2.0-85201430078
通讯作者地址	[Li, Xiaokun;Pan, Xuebo;Wang, Cong]Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Medicine (miscellaneous);Biochemistry, Genetics and Molecular Biology (all);Agricultural and Biological Sciences (all)
SCOPUS_ID	SCOPUS_ID:85201430078
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217423
专题	药学院（分析测试中心）附属第一医院附属第一医院_泌尿外科
通讯作者	Li, Xiaokun; Pan, Xuebo; Wang, Cong
作者单位	1.Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China; 2.Zhejiang Univ, Affiliated Sir Run Run Shaw Hosp, Sch Med, Dept Head & Neck Surg, Hangzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 1, Dept Urol, Wenzhou, Zhejiang, Peoples R China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Lin, Hui,Lin, Shuaijun,Shi, Liuhong,et al. FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells[J]. Communications Biology,2024,7(1).
APA	Lin, Hui., Lin, Shuaijun., Shi, Liuhong., Xu, Guangsen., Lin, Manjie., ... & Wang, Cong. (2024). FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells. Communications Biology, 7(1).
MLA	Lin, Hui,et al."FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells".Communications Biology 7.1(2024).