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MCCC2 promotes HCC development by supporting leucine oncogenic function.

Yu-Yan Chen1,2, Xue-Ning Zhang3, Chen-Zhou Xu4

  • 1Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, China.

Cancer Cell International
|January 7, 2021
PubMed
Summary
This summary is machine-generated.

Methylcrotonoyl-CoA carboxylase 2 (MCCC2) drives hepatocellular carcinoma (HCC) progression by influencing leucine metabolism and promoting cell proliferation. Targeting MCCC2 and leucine metabolism offers a potential new strategy for HCC treatment.

Keywords:
ERKHepatocellular carcinomaMCCC2leucinemetabolism

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Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Pathways

Background:

  • Methylcrotonoyl-CoA carboxylase 2 (MCCC2) is implicated in tumor development.
  • The role of MCCC2 and its relationship with leucine in hepatocellular carcinoma (HCC) progression remain unclear.

Purpose of the Study:

  • To investigate the prognostic value and functional role of MCCC2 in HCC.
  • To explore the correlation between MCCC2, leucine metabolism, and HCC progression.

Main Methods:

  • Prognostic value assessed using Gepia database.
  • MCCC2 expression and localization determined by western blot and immunofluorescence.
  • Cell proliferation, migration, and invasion assays (flow cytometry, CCK-8, transwell).
  • Mass spectrometry for functional prediction.

Main Results:

  • MCCC2 expression is elevated in HCC tissues and correlates with poor patient outcomes.
  • MCCC2 knockdown inhibits HCC cell proliferation, migration, and invasion in vitro and in vivo.
  • MCCC2-expressing HCC cells are resistant to leucine deprivation; leucine deprivation inhibits proliferation in MCCC2-present cells.
  • MCCC2 knockdown reduces glycolysis markers, glucose consumption, lactate secretion, and acetyl-CoA levels.
  • MCCC2 promotes ERK activation and is associated with protein and energy metabolism pathways.

Conclusions:

  • MCCC2 plays a critical role in HCC development.
  • The leucine metabolism pathway represents a potential novel therapeutic target for HCC.