RACK1 Promotes Self-Renewal and Chemoresistance of Cancer Stem Cells in Human Hepatocellular Carcinoma through Stabilizing Nanog

Theranostics
Junxia CaoJiyan Zhang

Abstract

Targeting cancer stem cells (CSCs) has been proposed as a new strategy to eradicate malignancies, including hepatocellular carcinoma (HCC). However, the mechanisms by which CSCs sustain their self-renewal and chemoresistance remain elusive. Nanog is a master transcriptional regulator of stemness, especially in CSCs. Its expression is tightly regulated by the ubiquitin-proteasome system in embryonic stem cells (ESCs). Whether the suppression of Nanog ubiquitination contributes to its over-expression in CSCs has not been explored. In addition, the role of receptor for activated C kinase 1 (RACK1), an adaptor protein implicated in HCC growth, in liver CSC-like traits remains to be determined. Methods: In vitro and in vivo assays were performed to investigate the role of RACK1 in liver CSC-like phenotype and murine ESC function. How RACK1 regulates Nanog expression was explored by immunoblotting and immunohistochemistry. The interaction of RACK1 with Nanog and the consequent effects on Nanog ubiquitination and stemness were then analyzed. Results: RACK1 promotes self-renewal and chemoresistance of human liver CSCs and maintains murine ESC function. Consistently, RACK1 enhances the expression of Nanog in human HCC cells and murine E...Continue Reading

Citations

Jan 11, 2019·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Shyam Menon, Ray Mathew
May 7, 2019·Cancers·Kwei-Yan LiuShen-Nien Wang
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Juan Li, Ying Zhu
Apr 9, 2021·Archives of Biochemistry and Biophysics·Jun LiJiongjiong Lu
May 4, 2021·Frontiers in Pharmacology·Yuanqi LiuChunfang Zhang
Jul 16, 2021·Drug Discovery Today·Abdul Q KhanMartin Steinhoff
Feb 12, 2020·Molecular Therapy. Nucleic Acids·Tao HanZhendong Zheng

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Methods Mentioned

BETA
ubiquitination
pull-down
immunoprecipitation
confocal microscopy
PCR
flow cytometry
coimmunoprecipitation
transfection
nuclear translocation

Software Mentioned

SPSS

Related Concepts