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Updated: Aug 20, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

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Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis

Sujin Park1, Dirk Mossmann1, Qian Chen2

  • 1Biozentrum, University of Basel, 4056 Basel, Switzerland.

Molecular Cell
|November 18, 2022
PubMed

Insights

Decreased acetyl-coenzyme A (acetyl-CoA) synthesis in liver cancer (HCC) leads to reduced protein acetylation and promotes tumor growth. Repressing acetyl-CoA synthesis via TEAD2 and E2A links metabolism reprogramming to cancer progression.

Area of Science:

  • Metabolic pathways
  • Cancer biology
  • Epigenetics

Background:

  • Acetyl-coenzyme A (acetyl-CoA) is crucial for cellular processes, but its role in cancer, particularly hepatocellular carcinoma (HCC), is not well understood.
  • Dysregulation of acetyl-CoA metabolism may contribute to cancer development and progression.

Purpose of the Study:

  • To investigate acetyl-CoA synthesis and protein acetylation in hepatocellular carcinoma (HCC).
  • To elucidate the mechanisms by which acetyl-CoA metabolism is altered in HCC and its impact on cancer biology.

Main Methods:

  • Analysis of acetyl-CoA levels and protein acetylation in a mouse model and patient samples of HCC.
  • Transcriptional profiling to identify altered acetyl-CoA biosynthesis pathways.
  • Investigating the role of transcription factors TEAD2 and E2A in regulating acetyl-CoA synthesis.

Main Results:

  • HCC exhibits decreased acetyl-CoA levels due to the transcriptional downregulation of all six acetyl-CoA biosynthesis pathways.
  • Hypo-acetylation of non-histone proteins, including metabolic enzymes, was observed in HCC.
  • Repression of acetyl-CoA synthesis by TEAD2 and E2A promoted oncogenic dedifferentiation and proliferation.
  • Knockdown of TEAD2 and E2A restored acetyl-CoA levels and inhibited tumor growth.

Conclusions:

  • Transcriptional reprogramming of acetyl-CoA metabolism is causally linked to cancer progression in HCC.
  • TEAD2 and E2A are novel regulators of acetyl-CoA synthesis that drive oncogenic dedifferentiation and proliferation.
  • Targeting acetyl-CoA synthesis represents a potential therapeutic strategy for HCC.
Keywords:
E2AHCCTEAD2acetyl-CoA metabolismdedifferentiationhepatocellular carcinomaprotein acetylationtranscriptional reprogramming

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