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Sci Rep. 2017 Sep 14;7(1):11653. doi: 10.1038/s41598-017-12037-8.

SOX9 Regulates Cancer Stem-Like Properties and Metastatic Potential of Single-Walled Carbon Nanotube-Exposed Cells.

Author information

1
West Virginia University Cancer Institute, West Virginia University, Morgantown, WV, 26506, United States.
2
Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, 26506, United States.
3
Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
4
Allergy and Clinical Immunology Branch, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, United States.
5
Department of Chemical Engineering, West Virginia University, Morgantown, WV, 26506, United States.
6
Department of Biochemistry, West Virginia University, Morgantown, WV, 26506, United States.
7
West Virginia University Cancer Institute, West Virginia University, Morgantown, WV, 26506, United States. yrojan@hsc.wvu.edu.
8
Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV, 26506, United States. yrojan@hsc.wvu.edu.

Abstract

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.

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