NDLI: Arsenite inhibits the function of CD133$^{+}$ CD13$^{+}$ liver cancer stem cells by reducing PML and Oct4 protein expression

Content Provider	Springer Nature Link
Author	Tang, Huaming Jin, Yukai Jin, Shilong Tan, Zhiming Peng, Zhang Kuang, Yuanli
Copyright Year	2016
Abstract	Cancer stem cells (CSCs) can form new tumors and contribute to post-operative recurrence and metastasis. We showed that CD133$^{+}$CD13$^{+}$ hepatocytes isolated from HuH7 cells and primary HCC cells display biochemical and functional characteristics typical of CSCs, suggesting that CD133$^{+}$CD13$^{+}$ hepatocytes in primary HCC tumors function as CSCs. We also found that arsenite treatment reduced the viability and stemness of CD133$^{+}$CD13$^{+}$ hepatocytes, enhanced the sensitivity of HuH7 cells to pirarubicin, and reduced the tumorigenicity of CD133$^{+}$CD13$^{+}$ hepatocytes xenografts in mice. The effects of sodium arsenite treatment in CD133$^{+}$CD13$^{+}$ hepatocytes were mediated by the post-transcriptional suppression of PML expression and the inhibition of Oct4, Sox2, and Klf4 expression at the transcriptional level. Incomplete rescue of Oct4 expression in arsenic-treated cells ectopically expressing an siRNA-resistant PML transcript suggested that OCT4 regulation in liver CSCs involves other factors in addition to PML. Our findings provide evidence of a specific role for PML in regulating Oct4 levels in liver CSCs and highlight the clinical importance of arsenic for improving the efficacy of other chemotherapeutic agents and the prevention of post-operative HCC recurrence and metastasis.
Starting Page	14103
Ending Page	14115
Page Count	13
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-08-12
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Arsenite,CD133$^{+}$ CD13$^{+}$ Liver cancer stem cells PML Oct4 Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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