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

  • 0Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Nature Chemical Biology +

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March 28, 2024

|

March 28, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Fructose-1,6-bisphosphatase 1 (FBP1) inhibits telomerase activity by dephosphorylating TERT, reducing telomere length and suppressing tumor growth. FBP1 deficiency promotes cancer cell immortality.

Area Of Science

  • Biochemistry
  • Oncology
  • Molecular Biology

Background

  • Telomere dysfunction is a hallmark of cancer and aging.
  • Telomerase activity is crucial for maintaining telomere length and cellular immortality.
  • The regulation of telomerase in cancer cells is complex and not fully understood.

Purpose Of The Study

  • To investigate the role of fructose-1,6-bisphosphatase 1 (FBP1) in regulating telomerase activity.
  • To explore the potential of FBP1 as a therapeutic target for cancer treatment.

Main Methods

  • Investigated the interaction between FBP1 and telomerase reverse transcriptase (TERT).
  • Assessed the effect of FBP1 on TERT phosphorylation and nuclear translocation.
  • Utilized lipid nanoparticle-mediated delivery of FBP1 mRNA in mouse models.
  • Correlated FBP1 expression with TERT pSer227 levels and patient prognosis in cancer specimens.

Main Results

  • FBP1 dephosphorylates TERT at Ser227, inhibiting its nuclear translocation and telomerase activity.
  • FBP1 expression suppresses tumor cell proliferation, growth, and induces senescence.
  • Lipid nanoparticle-delivered FBP1 mRNA inhibited liver tumor growth.
  • FBP1 levels inversely correlate with TERT pSer227 and poor prognosis in renal and hepatocellular carcinoma.

Conclusions

  • FBP1 acts as a negative regulator of telomerase activity through its protein phosphatase function.
  • FBP1 deficiency contributes to cancer cell immortality by allowing TERT activation.
  • FBP1 represents a novel therapeutic target for modulating telomere length and treating cancer.

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