RRC ID 81235
Author Fukushi D, Shibuya-Takahashi R, Mochizuki M, Fujimori H, Kogure T, Sugai T, Iwai W, Wakui Y, Abue M, Murakami K, Nakamura Y, Yasuda J, Yamaguchi K, Sugamura K, Shibata C, Katayose Y, Satoh K, Tamai K.
Title BEX2 is required for maintaining dormant cancer stem cell in hepatocellular carcinoma.
Journal Cancer Sci
Abstract Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC.
Volume 112(11)
Pages 4580-4592
Published 2021-11-1
DOI 10.1111/cas.15115
PMID 34424582
PMC PMC8586677
MeSH Aged Aldehyde Dehydrogenase / metabolism Animals Antineoplastic Agents / pharmacology Carcinoma, Hepatocellular / drug therapy Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cholangiocarcinoma / metabolism Cisplatin / pharmacology Female Gene Silencing Humans Liver Neoplasms / drug therapy Liver Neoplasms / metabolism* Liver Neoplasms / pathology Male Mice Neoplastic Stem Cells / metabolism* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Organoids Prognosis Spheroids, Cellular
IF 4.966
Resource
Human and Animal Cells HuCCT1(RCB1960)