KAT2A affects tumor metabolic reprogramming in colon cancer progression through epigenetic activation of E2F1

Xiaofeng Han1, Jie Chen2

  • 1Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100043, People's Republic of China.

Human Cell
|May 17, 2022
PubMed

Insights

Lysine acetyltransferase 2A (KAT2A) drives colon cancer progression by altering cell metabolism and promoting metastasis. Targeting KAT2A may offer a new therapeutic strategy for colon cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Lysine acetyltransferase 2A (KAT2A) is linked to cancer, but its role in colon cancer (CC) initiation and progression is unclear.
  • Metabolic reprogramming is a key feature of cancer development.

Purpose of the Study:

  • To investigate the role of KAT2A in metabolic reprogramming in colon cancer.
  • To elucidate the molecular mechanisms by which KAT2A influences colon cancer progression.

Main Methods:

  • Overexpression analysis of KAT2A in CC tissues.
  • Assessment of CC cell proliferation, migration, invasion, and epithelial-mesenchymal transition.
  • Measurement of cellular glycolysis and mitochondrial function.
  • Chromatin immunoprecipitation (ChIP) assays to verify KAT2A binding to E2F1.
  • Rescue experiments involving E2F1 downregulation.
  • In vivo mouse models for tumorigenesis and metastasis studies.

Main Results:

  • KAT2A is overexpressed in CC and associated with metastasis.
  • KAT2A enhances CC cell proliferation, migration, invasion, and EMT.
  • KAT2A elevates cellular glycolysis and mitochondrial stress.
  • KAT2A activates E2F transcription factor 1 (E2F1) via H3K9 acetylation.
  • E2F1 downregulation reverses KAT2A-induced metabolic and cellular changes.
  • KAT2A/E2F1 signaling promotes tumor growth and lung metastasis in mice.

Conclusions:

  • KAT2A plays a significant role in colon cancer progression by modulating E2F1 acetylation and promoting metabolic reprogramming.
  • KAT2A/E2F1 axis is crucial for colon cancer cell tumorigenesis and metastasis.
  • Targeting KAT2A presents a potential therapeutic strategy for colon cancer.

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