The SOX9-Aldehyde Dehydrogenase Axis Determines Resistance to Chemotherapy in Non-Small-Cell Lung Cancer

Details

• Personal Author:
  Kiratipaiboon C ; Rojanasakul LW ; Rojanasakul Y ; Voronkova MA
• Description:
  Chemotherapy resistance and tumor relapse are the major contributors to low patient survival, and both have been largely attributed to cancer stem-like cells (CSCs) or tumor initiating cells (TICs). Moreover, most conventional therapies are not effective against CSCs, which necessitates the discovery of CSC-specific biomarkers and drug targets. Here, we demonstrated that the embryonic transcription factor SOX9 is an important regulator of acquired chemoresistance in non-small cell lung cancer (NSCLC). Our results show that SOX9 expression is elevated in NSCLC cells after treatment with the chemotherapeutic cisplatin and that overexpression of SOX9 correlates with worse overall survival in lung cancer patients. We further demonstrated that SOX9 knockdown increases cellular sensitivity to cisplatin, whereas its overexpression promotes drug resistance. Moreover, this transcription factor promotes stem-like properties of NSCLC cells and increases their ALDH activity, which was identified as the key mechanism of SOX9-induced chemoresistance. Finally, we showed that ALDH1A1 is a direct transcriptional target of SOX9 based on chromatin immunoprecipitation and luciferase reporter assays. Taken together, our novel findings on the role of SOX9-ALDH axis support the use of this CSC regulator as a prognostic marker of cancer chemoresistance and as a potential drug target for CSC therapy. [Description provided by NIOSH]
• Subjects:
  Enzymes Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: ALDH1A1 Cancer Stem-like Cells Chemoresistance Chemotherapy Enzyme Activity Gene Expression Gene Regulation Genes Lung Cancer SOX9 Stem Cells

  More +
• ISSN:
  0270-7306
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  40
• Issue:
  2
• NIOSHTIC Number:
  nn:20057787
• Citation:
  Mol Cell Biol 2020 Jan; 40(2):e00307-19
• Contact Point Address:
  Yon Rojanasakul, Department of Pharmaceutical Sciences and West Virginia University Cancer Institute, West Virginia University, Morgantown, West Virginia, USA
• Email:
  yrojan@hsc.wvu.edu
• CAS Registry Number:
  Cisplatin (CAS RN 15663-27-1)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0737726f4764226ac09400e98b93ba4cc6e430949d63b2ca3c0015db8cd0063ba83729e104445c714a10bec7aa7de95513ede11a4efa01f2be63a422d8bbad61
• Download URL:
  https://stacks.cdc.gov/view/cdc/215019/cdc_215019_DS1.pdf
• File Type:
  [PDF - 2.33 MB ]