SOX9 Regulates Cancer Stem-Like Properties and Metastatic Potential Exposed Cells

Details

• Personal Author:
  Castranova, Vincent ; Dinu CZ ; Luanpitpong S ; Riedel H ; Rofanasakul LW ; Rojanasakul Y ; Voronkova MA
• Description:
  Engineered nanomaterials hold great promise for the future development of innovative products but their adverse health effects are a major concern. Recent studies have indicated that certain nanomaterials, including carbon nanotubes (CNTs), may be carcinogenic. However, the underlying mechanisms behind their potential malignant properties remain unclear. In this study, we linked SOX9, a stem cell associated transcription factor, to the neoplastic-like properties of human lung epithelial cells chronically exposed to a low-dose of single-walled carbon nanotubes (SWCNTs). We found that SOX9 is upregulated in SWCNT-exposed cells, which is consistent with their abilities to induce tumor formation and metastasis in vivo. We therefore hypothesized that SOX9 overexpression may be responsible for the neoplastic-like phenotype observed in our model. Indeed, SOX9 knockdown inhibited anchorage-independent cell growth in vitro and lung colonization in vivo in a mouse xenograft model. SOX9 depletion also suppressed the formation of cancer stem-like cells (CSCs), as determined by tumor sphere formation and aldehyde dehydrogenase (ALDH) activity (Aldefluor) assays. Furthermore, SOX9 knockdown suppressed tumor metastasis and the expression of the stem cell marker ALDH1A1. Taken together, our findings provide a mechanistic insight into SWCNT-induced carcinogenesis and the role of SOX9 in CSC regulation and metastasis. [Description provided by NIOSH]
• Subjects:
  Aldehydes Animals Carcinogens Cells, Cultured Formaldehyde Laboratories Lung Neoplasms Occupational Health Respiratory System Safety

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• Keywords:
  Carbon Nanotubes Carcinogenicity Cell Cultures Health Effects Humans In Vitro Study In Vivo Study Laboratory Animals Lung Cells Metastasis Models Nanomaterials Nanotechnology Stem Cells Tumors

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• ISSN:
  2045-2322
• 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:
  7
• NIOSHTIC Number:
  nn:20050456
• Citation:
  Sci Rep 2017 Sep; 7:11653
• Contact Point Address:
  Yon Rojanasakul, West Virginia University Cancer Institute, West Virginia University, Morgantown, WV, 26506
• Email:
  yrojan@hsc.wvu.edu
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Scientific Reports
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6cd3e2d1be665d488f373e514f83ceccc39c16f214c88f7e12918097415c095ceee7566063bb0e5bbe9a88e746c63705f09b12519f855bb9c9fb05f2b8420934
• Download URL:
  https://stacks.cdc.gov/view/cdc/210785/cdc_210785_DS1.pdf
• File Type:
  [PDF - 8.59 MB ]