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Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma

  • 0Senior Department of Urology, The Third Medical Centre of PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China.
Experimental Cell Research +

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February 19, 2024

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February 19, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Phosphatidylserine decarboxylase 1 (PSAT1) is a key enzyme in serine metabolism. This study reveals PSAT1 as a prognostic biomarker and therapeutic target in clear cell renal cell carcinoma (ccRCC), impacting tumor growth and drug resistance.

Area Of Science

  • Biochemistry
  • Oncology
  • Metabolic Reprogramming

Background

  • Serine metabolism reprogramming is linked to cancer development.
  • Phosphatidylserine decarboxylase 1 (PSAT1) is a prognostic marker in several cancers, but its role in clear cell renal cell carcinoma (ccRCC) is unknown.

Purpose Of The Study

  • To investigate the expression and function of PSAT1 in ccRCC.
  • To evaluate PSAT1 as a prognostic biomarker and therapeutic target in ccRCC.

Main Methods

  • Analysis of TCGA database and clinical ccRCC specimens.
  • In vitro functional experiments (cell proliferation, migration, invasion, apoptosis assays).
  • RNA sequencing and xenograft mouse models.
  • Assessment of drug resistance to sunitinib.

Main Results

  • PSAT1 expression is lower in ccRCC tumor tissue than normal tissue but increases with ccRCC stage and grade.
  • Elevated PSAT1 expression correlates with unfavorable prognosis in ccRCC patients.
  • PSAT1 depletion inhibits ccRCC cell proliferation, migration, and invasion while promoting apoptosis.
  • PSAT1 inhibition reduces tumor growth, metastasis, and drug resistance in ccRCC models.
  • Targeting PSAT1 enhances sensitivity to sunitinib in drug-resistant ccRCC cells.

Conclusions

  • PSAT1 is an independent prognostic biomarker for advanced ccRCC.
  • PSAT1 represents a potential therapeutic target for ccRCC, particularly in overcoming drug resistance.

Keywords:

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