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Int J Biol Sci. 2019 May 11;15(6):1252-1260. doi: 10.7150/ijbs.28235. eCollection 2019.

Nuclear CD44 Mediated by Importin β Participated in Naïve Genes Transcriptional Regulation in C3A-iCSCs.

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Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Beijing Cellonis Biotechnologies Co. Ltd, Zhongguancun Bio-Medicine Park, Beijing, People's Republic of China.
State Key Laboratory of Organ Failure Research, Co-Innovation Center for Organ Failure Research, Guangdong Provincial Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Medical Center of Human Reproduction, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100069, China.


CD44 is one of biomarkers of liver cancer stem cells (CSCs). The investigation of mechanism of CD44 translocation helps to uncover new molecular pathways participated in the regulation of various cellular processes in CSCs. In the present study, we observed the translocation of CD44 from cytoplasm to nuclear in the reprogramming process of C3A cells, full-length CD44 presented in the nucleus of liver iCSCs. CD44 was bound with importin β and transportin 1 in liver iCSCs. Inhibition of importin β transport leads to reduction of CD44 in the nucleus. Translocation of CD44 is also influenced by importin α. Besides, overexpression of naïve pluripotent genes, KLF2, KLF5, DNMT3L, GBX2, ZFP42, ESRRB and DPPA4 were found in liver iCSCs. Inhibition of CD44 leads to the reduction of these naïve genes. Luciferase and chromatin immunoprecipitation (ChIP) assays further identified nuclear CD44 bound to the promoter regions of naïve genes, KLF2, KLF5, and ESRRB functioned as transcriptional activators in liver iCSCs. Our present work provides new insight into the dynamic states and functions of CD44 in iCSCs.


CD44; importin β; liver iCSCs; naïve gene

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