Role of AhR in regulating cancer stem cell–like characteristics in choriocarcinoma

作者：Chenchun Wu, Shuran Yu, Qianxia Tan, Peng Guo, Huining Liu · 发表于：Cell Cycle · 年份：2018 · DOI：10.1080/15384101.2018.1535219 · 被引用次数：31 · 研究领域：Epigenetics and DNA Methylation、Renal and related cancers、Cancer Cells and Metastasis

Choriocarcinoma is sensitive to chemotherapy. However, drug resistance has become one of the major problems in recent years. Previous studies have shown that many tumors contained a small fraction of cells that exhibited enhanced tumor initiating potential and stem cell-like properties. It is hypothesized that cancer stem cells (CSCs) are organized in a cellular hierarchy. They also have the qualities of self-renewal, chemoresistance, and so on. The identification of CSCs in choriocarcinoma and the mechanism contributing to their qualities remain largely unknown. This study focused on the role of AhR, a transcription factor abundantly expressed in many different types of cancer, in the regulation of the expansion of choriocarcinoma CSCs and the exact molecular mechanisms. Spheroid cells isolated from choriocarcinoma in serum-free conditions have stem cell-like characteristics. The expression and nuclear translocation of AhR were markedly elevated in spheroid cells. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly increased the spheroid-forming efficiency, chemotherapy resistance, and ability to form tumor xenografts of the cells, whereas AhR knockdown, using short hairpin RNA (shRNA), dramatically reduced stem cell properties. Mechanistically, activating the β-catenin pathway might be an essential biological function of AhR during the regulation of the CSC characteristics. This study also identified ABCG2, which plays an important role in CSCs, as...