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ALDH2 Repression Promotes Lung Tumor Progression via Accumulated Acetaldehyde and DNA Damage

Kaimi Li1, Wenzheng Guo1, Zhanming Li2

  • 1Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Neoplasia (New York, N.Y.)
|May 10, 2019
PubMed

Insights

Aldehyde dehydrogenase 2 (ALDH2) normally detoxifies acetaldehyde. Its reduced function in lung cancer promotes tumor growth and migration by increasing acetaldehyde, suggesting ALDH2 activation as a potential cancer therapy.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Aldehyde dehydrogenase 2 (ALDH2) is crucial for detoxifying acetaldehyde (ACE).
  • ALDH2 dysfunction is implicated in various diseases, including cancer, but its role in tumor progression is not fully understood.

Purpose of the Study:

  • To investigate the biological function and molecular mechanisms of ALDH2 in lung adenocarcinoma progression.
  • To explore the potential of ALDH2 activation as a therapeutic strategy for lung cancer.

Main Methods:

  • Analysis of ALDH2 expression in lung adenocarcinoma patient data.
  • In vitro studies involving ALDH2 overexpression and knockdown in lung adenocarcinoma cell lines.
  • In vivo studies using Aldh2-knockout mouse models.
  • Treatment of cell lines with the ALDH2 agonist Alda-1.

Main Results:

  • ALDH2 repression correlated with poor prognosis in lung adenocarcinoma.
  • ALDH2 overexpression suppressed proliferation, stemness, and migration; knockdown enhanced these features.
  • ALDH2 repression led to ACE accumulation, which promoted cell migration and DNA damage.
  • ACE accumulation and DNA damage were observed in Aldh2-knockout mouse lungs.
  • Alda-1 treatment inhibited malignant cell features.

Conclusions:

  • ALDH2 plays a tumor-suppressive role in lung adenocarcinoma by detoxifying ACE and preventing DNA damage.
  • Activating ALDH2, for example, with Alda-1, may represent a novel therapeutic approach for lung cancer.

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