1. Academic Validation
  2. Methylation of TMEM176A, a key ERK signaling regulator, is a novel synthetic lethality marker of ATM inhibitors in human lung cancer

Methylation of TMEM176A, a key ERK signaling regulator, is a novel synthetic lethality marker of ATM inhibitors in human lung cancer

  • Epigenomics. 2021 Sep;13(17):1403-1419. doi: 10.2217/epi-2021-0217.
Hongxia Li 1 2 Weili Yang 1 Meiying Zhang 1 Tao He 3 Fuyou Zhou 4 James G Herman 5 Liming Hu 2 Mingzhou Guo 1 6 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
  • 2 Faculty of Environmental & Life Science, Beijing Key Laboratory of Environmental & Oncology, Beijing University of Technology, Beijing, 100124, China.
  • 3 Department of Pathology, Characteristic Medical Center of The Chinese People's Armed Police Force, Tianjin, 300162, China.
  • 4 Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, 455000, Henan, China.
  • 5 The Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 2.18/Research, Pittsburgh, PA 15213, USA.
  • 6 Henan Key Laboratory for Esophageal Cancer Research, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, China.
  • 7 State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853, China.
Abstract

Aim: The role of TMEM176A methylation in lung Cancer and its therapeutic application remains unclear. Materials and methods: Nine lung Cancer cell lines and 123 cases of Cancer tissue samples were employed. Results:TMEM176A was methylated in 53.66% of primary lung Cancer. Restoration of TMEM176A expression induced cell Apoptosis and G2/M phase arrest, and inhibited colony formation, cell proliferation, migration and invasion. TMEM176A suppressed H1299 cell xenograft growth in mice. Methylation of TMEM176A activated ERK signaling and sensitized H1299 and H23 cells to AZD0156, an ATM Inhibitor. Conclusion: The expression of TMEM176A is regulated by promoter region methylation. Methylation of TMEM176A is a potential lung Cancer diagnostic marker and a novel synthetic lethal therapeutic marker for AZD0156.

Keywords

AZD0156; DNA methylation; ERK pathway; TMEM176A; synthetic lethality.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50846
    99.27%, ERK1/2 Inhibitor
    ERK