The Evolving Concept of Liver Cancer Stem Cells

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2017 Feb 1

PMID 28137313

Citations 138

Authors

Kouki Nio

Taro Yamashita

Shuichi Kaneko

Affiliations

Soon will be listed here.

Abstract

Liver cancer is an often fatal malignant tumor with a high recurrence rate and chemoresistance. The major malignant phenotypes of cancer, including recurrence, metastasis, and chemoresistance, are related to the presence of cancer stem cells (CSCs). In the past few decades, CSCs have been identified and characterized in many tumors including liver cancer. Accumulated evidence has revealed many aspects of the biological behavior of liver CSCs and the mechanism of their regulation. Based on these findings, a number of studies have investigated eradication of liver CSCs. This review focuses on the recent advances in our understanding of the biology of liver CSCs and the development of strategies for their treatment.

Citing Articles

Biological roles and clinical applications of EpCAM in HCC.

Liu P, Zhang Q, Liu F Discov Oncol. 2025; 16(1):319.

PMID: 40087210 DOI: 10.1007/s12672-025-02095-0.

Molecular subtyping combined with multiomics analysis to study correlation between TACE refractoriness and tumor stemness in hepatocellular carcinoma.

He Q, Xiong Y, Yang X, Yu Y, Chen Z Discov Oncol. 2025; 16(1):197.

PMID: 39961903 PMC: 11832877. DOI: 10.1007/s12672-025-01955-z.

Novel insights into the impact of liver inflammatory responses on primary liver cancer development.

Ait-Ahmed Y, Lafdil F Liver Res. 2025; 7(1):26-34.

PMID: 39959704 PMC: 11791919. DOI: 10.1016/j.livres.2023.01.001.

PGD2/PTGDR2 signaling pathway affects the self-renewal capacity of gastric cancer stem cells by regulating ATG4B ubiquitination.

Zhang Q, Tian H, Ge K, Wang F, Gao P, Chen A Front Oncol. 2025; 14():1496050.

PMID: 39777337 PMC: 11703842. DOI: 10.3389/fonc.2024.1496050.

MicroRNA Profiling of PRELI-Modulated Exosomes and Effects on Hepatic Cancer Stem Cells.

Kim B Int J Mol Sci. 2025; 25(24.

PMID: 39769068 PMC: 11678812. DOI: 10.3390/ijms252413299.

References

Haraguchi N, Ishii H, Mimori K, Tanaka F, Ohkuma M, Kim H . CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest. 2010; 120(9):3326-39. PMC: 2929722. DOI: 10.1172/JCI42550. View

Shackleton M, Quintana E, Fearon E, Morrison S . Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell. 2009; 138(5):822-9. DOI: 10.1016/j.cell.2009.08.017. View

Magee J, Piskounova E, Morrison S . Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012; 21(3):283-96. PMC: 4504432. DOI: 10.1016/j.ccr.2012.03.003. View

Muramatsu S, Tanaka S, Mogushi K, Adikrisna R, Aihara A, Ban D . Visualization of stem cell features in human hepatocellular carcinoma reveals in vivo significance of tumor-host interaction and clinical course. Hepatology. 2013; 58(1):218-28. DOI: 10.1002/hep.26345. View

Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao H . Human hepatic stem cells from fetal and postnatal donors. J Exp Med. 2007; 204(8):1973-87. PMC: 2118675. DOI: 10.1084/jem.20061603. View

Song W, Li H, Tao K, Li R, Song Z, Zhao Q . Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 2008; 62(8):1212-8. DOI: 10.1111/j.1742-1241.2008.01777.x. View

Lin L, Amin R, Gallicano G, Glasgow E, Jogunoori W, Jessup J . The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling. Oncogene. 2009; 28(7):961-72. PMC: 2703464. DOI: 10.1038/onc.2008.448. View

Lau E, Lo J, Cheng B, Ma M, Lee J, Ng J . Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling. Cell Rep. 2016; 15(6):1175-89. DOI: 10.1016/j.celrep.2016.04.019. View

Shan J, Shen J, Liu L, Xia F, Xu C, Duan G . Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology. 2012; 56(3):1004-14. DOI: 10.1002/hep.25745. View

10.

Ma S, Chan K, Hu L, Lee T, Wo J, Ng I . Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007; 132(7):2542-56. DOI: 10.1053/j.gastro.2007.04.025. View

11.

Xu X, Liu R, Zhang X, Huang L, Chen F, Fei Q . DLK1 as a potential target against cancer stem/progenitor cells of hepatocellular carcinoma. Mol Cancer Ther. 2012; 11(3):629-38. DOI: 10.1158/1535-7163.MCT-11-0531. View

12.

Yamashita T, Forgues M, Wang W, Kim J, Ye Q, Jia H . EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 2008; 68(5):1451-61. DOI: 10.1158/0008-5472.CAN-07-6013. View

13.

Qian M, Wang D, Chen H, Cheng Y . Detection of single cell heterogeneity in cancer. Semin Cell Dev Biol. 2016; 64:143-149. DOI: 10.1016/j.semcdb.2016.09.003. View

14.

Tang Y, Kitisin K, Jogunoori W, Li C, Deng C, Mueller S . Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci U S A. 2008; 105(7):2445-50. PMC: 2268156. DOI: 10.1073/pnas.0705395105. View

15.

Liu M, Chen L, Ma N, Chow R, Song Y, Chan T . CHD1L promotes lineage reversion of hepatocellular carcinoma through opening chromatin for key developmental transcription factors. Hepatology. 2016; 63(5):1544-59. DOI: 10.1002/hep.28437. View

16.

Maude S, Frey N, Shaw P, Aplenc R, Barrett D, Bunin N . Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371(16):1507-17. PMC: 4267531. DOI: 10.1056/NEJMoa1407222. View

17.

Liu L, Liu C, Zhang Q, Shen J, Zhang H, Shan J . SIRT1-mediated transcriptional regulation of SOX2 is important for self-renewal of liver cancer stem cells. Hepatology. 2016; 64(3):814-27. DOI: 10.1002/hep.28690. View

18.

Yamashita T, Budhu A, Forgues M, Wang X . Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res. 2007; 67(22):10831-9. DOI: 10.1158/0008-5472.CAN-07-0908. View

19.

Heppner G . Tumor heterogeneity. Cancer Res. 1984; 44(6):2259-65. View

20.

Sekiya S, Suzuki A . Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest. 2012; 122(11):3914-8. PMC: 3484442. DOI: 10.1172/JCI63065. View