Research Papers:

CWP232228 targets liver cancer stem cells through Wnt/β‑catenin signaling: a novel therapeutic approach for liver cancer treatment

Ji‑Young Kim, Hwa‑Yong Lee, Kwan‑Kyu Park, Yang‑Kyu Choi, Jeong‑Seok Nam and In‑Sun Hong _

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Oncotarget. 2016; 7:20395-20409. https://doi.org/10.18632/oncotarget.7954

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Ji-Young Kim1,2,*, Hwa-Yong Lee3,*, Kwan-Kyu Park4, Yang-Kyu Choi2, Jeong-Seok Nam5, In-Sun Hong6,7

1Center of Animal Care and Use, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea

2Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Korea

3The Faculty of Liberal Arts, Jungwon University, Chungbuk, Republic of Korea

4Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea

5School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea

6Laboratory of Stem Cell Research, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea

7Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Jeong-Seok Nam, e-mail: [email protected]

In-Sun Hong, e-mail: [email protected]

Keywords: CWP232228, cancer stem cells, Wnt/β-catenin signaling, CD133, ALDH

Received: September 11, 2015     Accepted: January 16, 2016     Published: March 07, 2016


Liver cancer stem cells (CSCs) are resistant to conventional chemotherapy and radiation, which may destroy tumor masses, but not all liver CSCs contribute to tumor initiation, metastasis, and relapse. In the present study, we showed that liver CSCs with elevated Wnt/β-catenin signaling possess much greater self-renewal and clonogenic potential. We further documented that the increased clonogenic potential of liver CSCs is highly associated with changes in Wnt/β-catenin signaling and that Wnt/β-catenin signaling activity is positively correlated with CD133 expression and aldehyde dehydrogenase (ALDH) enzymatic activity. Notably, the small molecule inhibitor CWP232228, which antagonizes the binding of β-catenin to TCF in the nucleus, inhibits Wnt/β-catenin signaling and depletes CD133+/ALDH+ liver CSCs, thus ultimately diminishing the self-renewal capacity of CSCs and decreasing tumorigenicity in vitro and in vivo. Taken together, our findings suggest that CWP232228 acts as a candidate therapeutic agent for liver cancer by preferentially targeting liver CSCs.

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