Fructose-1,6-bisphosphatase 1 dephosphorylates and inhibits TERT for tumor suppression.

Journal

Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976

Informations de publication

Date de publication:
27 Mar 2024
Historique:
received: 31 08 2023
accepted: 01 03 2024
medline: 28 3 2024
pubmed: 28 3 2024
entrez: 28 3 2024
Statut: aheadofprint

Résumé

Telomere dysfunction is intricately linked to the aging process and stands out as a prominent cancer hallmark. Here we demonstrate that telomerase activity is differentially regulated in cancer and normal cells depending on the expression status of fructose-1,6-bisphosphatase 1 (FBP1). In FBP1-expressing cells, FBP1 directly interacts with and dephosphorylates telomerase reverse transcriptase (TERT) at Ser227. Dephosphorylated TERT fails to translocate into the nucleus, leading to the inhibition of telomerase activity, reduction in telomere lengths, enhanced senescence and suppressed tumor cell proliferation and growth in mice. Lipid nanoparticle-mediated delivery of FBP1 mRNA inhibits liver tumor growth. Additionally, FBP1 expression levels inversely correlate with TERT pSer227 levels in renal and hepatocellular carcinoma specimens and with poor prognosis of the patients. These findings demonstrate that FBP1 governs cell immortality through its protein phosphatase activity and uncover a unique telomerase regulation in tumor cells attributed to the downregulation or deficiency of FBP1 expression.

Identifiants

DOI: 10.1038/s41589-024-01597-2 PMID: 38538923
pubmed: 38538923
doi: 10.1038/s41589-024-01597-2
pii: 10.1038/s41589-024-01597-2
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : China Postdoctoral Science Foundation
ID : 2021M692827

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Min Li (M)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Center, Zhejiang University, Hangzhou, China.

Zheng Wang (Z)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Center, Zhejiang University, Hangzhou, China.

Jingjing Tao (J)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Center, Zhejiang University, Hangzhou, China.
ORCID: 0000-0001-6473-3797

Hongfei Jiang (H)

The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao, China.

Huang Yang (H)

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.

Dong Guo (D)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Hong Zhao (H)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Xuxiao He (X)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Shudi Luo (S)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Xiaoming Jiang (X)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Center, Zhejiang University, Hangzhou, China.

Li Yuan (L)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Liwei Xiao (L)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Center, Zhejiang University, Hangzhou, China.

Haiyan He (H)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Rilei Yu (R)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
ORCID: 0000-0002-9611-3514

Jing Fang (J)

The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao, China.

Tingbo Liang (T)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
ORCID: 0000-0003-0143-3353

Zhengwei Mao (Z)

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.
ORCID: 0000-0001-7990-2856

Daqian Xu (D)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China. xudaqian@zju.edu.cn.
Cancer Center, Zhejiang University, Hangzhou, China. xudaqian@zju.edu.cn.
ORCID: 0000-0003-0478-2997

Zhimin Lu (Z)

Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China. zhiminlu@zju.edu.cn.
Cancer Center, Zhejiang University, Hangzhou, China. zhiminlu@zju.edu.cn.
ORCID: 0000-0002-2859-2736

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