期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 52, 期 3, 页码 872-880出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2018.4263
关键词
liver cancer; cancer stem cell; small ubiquitin-like modifiers; SUMOylation; connexin 43; herpes simplex virus 1 thymidine kinase; ganciclovir system
类别
资金
- National Natural Science Foundation of China [81471175, 1671246]
- Tianjin Health Bureau Science and Technology Projects [2014KY23, 2015KZ018]
Connexin 43 (Cx43) can be modified and regulated by small ubiquitin-like modifier (SUMO)1; however, its role in liver cancer stem cells is poorly understood. In this study, we found a significant difference in the expression of Cx43 and SUMO1 between cancer stem cells and non-cancer stem cells in liver cancer. In liver cancer stem cells, Cx43 was almost absent, although the level of SUMO1 was significantly higher than that in non-cancer stem cells. Further experiments confirmed that the conjugated site of Cx43 by SUMO1 was located in Lys-144 and Lys-237, both of which are highly conserved among species. By the co-expression of Cx43 and SUMO1 in cancer stem cells, the gap junction intercellular communication (GJIC) of liver cancer stem cells was obviously improved. Using this feature, we verified whether it could effectively increase the sensitivity of cancer stem cells to the herpes simplex virus 1 thymidine kinase (HSVtk) gene in combination with ganciclovir (GCV), a conventional chemotherapeutic drug, in vitro and in vivo. As expected, increasing the expression of Cx43 SUMOylation in liver cancer stem cells effectively enhanced their sensitivity to HSVtk/GCV. On the whole, this study revealed a novel method which may be used to effectively restore GJIC in cancer stem cells in liver cancer, which enhances their sensitivity to conventional chemotherapeutic drugs.
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