2. Academic Validation
  3. ALDH2 Repression Promotes Lung Tumor Progression via Accumulated Acetaldehyde and DNA Damage

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

  • Neoplasia. 2019 Jun;21(6):602-614. doi: 10.1016/j.neo.2019.03.008.
Kaimi Li 1,  Wenzheng Guo 1,  Zhanming Li 2,  Yang Wang 3,  Beibei Sun 4,  Dongliang Xu 1,  Jing Ling 3,  Hongyong Song 1,  Yueling Liao 1,  Tong Wang 1,  Bo Jing 1,  Min Hu 1,  Yanbin Kuang 5,  Qi Wang 5,  Feng Yao 6,  Aijun Sun 7,  Liang Zhu 3,  Lishun Wang 8,  Jiong Deng 9
Affiliations

Affiliations

  • 1 Key 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.
  • 2 Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai 201199, China.
  • 3 Department of Pharmacology and Chemical Biology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Translational Medical Research Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • 5 Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
  • 6 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • 7 Institute of Biomedical Sciences, Fudan University, Shanghai, China.
  • 8 Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai 201199, China. Electronic address: lishunwang@fudan.edu.cn.
  • 9 Key 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; Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: jiongdeng@shsmu.edu.cn.
PMID: 31071657 DOI: 10.1016/j.neo.2019.03.008
Abstract

The major role of aldehyde dehydrogenase 2 family (ALDH2) is to detoxify acetaldehyde (ACE) to non-toxic acetic acid. Many evidences suggest that ALDH2 dysfunction contributes to a variety of human diseases including Cancer. However, the biological function and molecular mechanism of ALDH2 in tumor progression remain elusive. In this study, we found that ALDH2 repression was associated with poor prognosis in lung adenocarcinoma. Overexpression of ALDH2 inhibited malignant features of lung adenocarcinoma cells, such as proliferation, stemness and migration, whereas ALDH2 knockdown increased these features. Mechanistically, ALDH2 repression led to accumulation of ACE; whereas ACE enhanced the migration features of lung adenocarcinoma cells, which was associated with increased DNA damage. Importantly, accumulated ACE and increased DNA damage were identified in Aldh2-knockout (KO) mouse lung tissues in vivo. Consistent with this concept, treatment of lung adenocarcinoma cells with ALDH2 Agonist Alda-1 suppressed the proliferation, stemness and migration features of lung adenocarcinoma cells. Thus, activating ALDH2, such as via its agonist, may provide a novel strategy for treatment of lung Cancer.

Figures
Products