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DEPDC1 as a metabolic target regulates glycolysis in renal cell carcinoma through AKT/mTOR/HIF1α pathway

Si-Chen Di1, Wen-Jin Chen1,2, Wei Yang1

  • 1Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Cell Death & Disease
|July 27, 2024
PubMed

Insights

DEPDC1 drives kidney cancer progression and drug resistance by increasing glycolysis. Targeting DEPDC1 may overcome tyrosine kinase inhibitor resistance in advanced renal cell carcinoma (RCC).

Area of Science:

  • Oncology
  • Metabolic Disease Research
  • Genomics

Background:

  • Renal cell carcinoma (RCC) is a metabolic disease with elevated glycolysis in advanced stages.
  • Tyrosine kinase inhibitor (TKI) therapy is a key treatment, but drug resistance is a significant challenge.

Purpose of the Study:

  • To investigate the role of glycolysis in advanced RCC prognosis and TKI resistance.
  • To identify novel therapeutic targets for overcoming TKI resistance in advanced RCC.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) on 14 RCC patients.
  • TCGA-KIRC and gene set analysis.
  • In vitro experiments with RCC cell lines.
  • Bulk RNA sequencing and non-targeted metabolomics.
  • Protein-level analysis and clinical tissue sample analysis (98 RCC patients).

Main Results:

  • scRNA-seq indicated glycolysis is crucial for poor prognosis and TKI resistance in RCC.
  • DEPDC1 was identified as a key target promoting malignant progression and glycolysis in KIRC.
  • Knockdown of DEPDC1 reversed TKI resistance in RCC cell lines.
  • DEPDC1 influences RCC glycolysis via the AKT/mTOR/HIF1α pathway.
  • DEPDC1 expression correlates with poor prognosis and metastasis in RCC patients.

Conclusions:

  • DEPDC1 promotes RCC progression and glycolysis, contributing to TKI resistance.
  • DEPDC1 is a potential therapeutic target for combination therapy (TKI + metabolic therapy) in advanced RCC with TKI resistance.

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