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Updated: Jul 16, 2025

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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Fatty Acid Oxidation Mediated by Malonyl-CoA Decarboxylase Represses Renal Cell Carcinoma Progression

Lijie Zhou1,2, Yongbo Luo1,2, Yuenan Liu3

  • 1Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Cancer Research
|September 20, 2023
PubMed

Insights

Malonyl-CoA decarboxylase (MLYCD) downregulation drives clear cell renal cell carcinoma (ccRCC) progression by promoting lipid synthesis. Restoring MLYCD enhances fatty acid oxidation, repressing tumor growth and improving treatment response.

Area of Science:

  • Oncology
  • Metabolic Pathways
  • Cancer Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) exhibits significant alterations in fatty acid metabolism, with increased lipid storage promoting tumor progression.
  • Understanding the molecular mechanisms behind altered fatty acid synthesis is crucial for developing effective ccRCC therapies.

Purpose of the Study:

  • To investigate the role of malonyl-CoA decarboxylase (MLYCD) in ccRCC fatty acid metabolism.
  • To explore the therapeutic potential of restoring MLYCD expression in ccRCC.

Main Methods:

  • Analysis of MLYCD expression in ccRCC patient data and correlation with prognosis.
  • Experimental manipulation of MLYCD expression in ccRCC cell lines and in vivo models.
  • Assessment of fatty acid synthesis, oxidation, lipid droplet accumulation, cellular homeostasis, reactive oxygen species, and ferroptosis.
  • Investigation of the regulatory mechanism involving HIF2α and eIF4G3.

Main Results:

  • MLYCD was found to be downregulated in ccRCC, with low expression correlating with poor patient prognosis.
  • Restoring MLYCD expression reduced malonyl-CoA levels, inhibited de novo fatty acid synthesis, and promoted fatty acid oxidation.
  • MLYCD-mediated fatty acid oxidation disrupted cellular homeostasis, increased reactive oxygen species, and induced ferroptosis.
  • Overexpression of MLYCD suppressed tumor growth, reversed sunitinib resistance, and was regulated by HIF2α-mediated translation inhibition.

Conclusions:

  • MLYCD-mediated fatty acid catabolism is essential for disrupting lipid homeostasis and repressing ccRCC progression.
  • Activating MLYCD-driven fatty acid metabolism represents a potential therapeutic strategy for ccRCC.

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