Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness
Epithelial cell adhesion molecule (EpCAM) is a biomarker for epithelial cell-derived tumors. However, the specific role of EpCAM itself in early-stage hepatocellular carcinoma progression remains unclear, and small molecules targeting EpCAM have not yet been reported. Here, the protein expression pr...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Compuscript Ltd
2025-01-01
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| Series: | Acta Materia Medica |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2024-0064 |
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| author | Lijuan Deng Lifang Zou Chunhong Zhou Fuqin Yang Fen Ouyang Yingru Zhu Huihui Cao Min Hu Xiaoshen Zhang Junshan Liu |
| author_facet | Lijuan Deng Lifang Zou Chunhong Zhou Fuqin Yang Fen Ouyang Yingru Zhu Huihui Cao Min Hu Xiaoshen Zhang Junshan Liu |
| author_sort | Lijuan Deng |
| collection | DOAJ |
| description | Epithelial cell adhesion molecule (EpCAM) is a biomarker for epithelial cell-derived tumors. However, the specific role of EpCAM itself in early-stage hepatocellular carcinoma progression remains unclear, and small molecules targeting EpCAM have not yet been reported. Here, the protein expression profile of EpCAM in tumor-adjacent regions was found to be higher than that in tumor regions, and to be positively associated with the progression of early-stage liver cancer, as well as high frequency of recurrence, cirrhosis, lymph node metastasis, microvascular invasion and cancer stemness, in 68 patients with hepatocellular carcinoma (HCC). In vitro , EpCAM enhanced cancer cell stemness, as reflected by increased abilities of proliferation, self-renewal, migration and invasion, which was counteracted by arenobufagin. Furthermore, arenobufagin inhibited the viability of Hep3B and Huh7 cells with IC 50 values of 36.4 nM and 123.4 nM after 72 h of treatment, respectively. Molecular docking data further indicated that arenobufagin binds EpCAM. Moreover, arenobufagin inhibited early progression of HCC through EpCAM in a zebrafish xenograft tumor model mimicking early-stage hepatocellular carcinoma without blood vessels in vivo . This study supports a tumor-promoting role of EpCAM in early-stage hepatocellular carcinoma by facilitating cancer stemness and suggests that arenobufagin might be promising candidate for EpCAM inhibition. |
| format | Article |
| id | doaj-art-6e83e15ca1e24aa6944288aecd21f14c |
| institution | Kabale University |
| issn | 2737-7946 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Compuscript Ltd |
| record_format | Article |
| series | Acta Materia Medica |
| spelling | doaj-art-6e83e15ca1e24aa6944288aecd21f14c2025-01-17T17:00:11ZengCompuscript LtdActa Materia Medica2737-79462025-01-0141829810.15212/AMM-2024-0064Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemnessLijuan DengLifang ZouChunhong ZhouFuqin YangFen OuyangYingru ZhuHuihui CaoMin HuXiaoshen ZhangJunshan LiuEpithelial cell adhesion molecule (EpCAM) is a biomarker for epithelial cell-derived tumors. However, the specific role of EpCAM itself in early-stage hepatocellular carcinoma progression remains unclear, and small molecules targeting EpCAM have not yet been reported. Here, the protein expression profile of EpCAM in tumor-adjacent regions was found to be higher than that in tumor regions, and to be positively associated with the progression of early-stage liver cancer, as well as high frequency of recurrence, cirrhosis, lymph node metastasis, microvascular invasion and cancer stemness, in 68 patients with hepatocellular carcinoma (HCC). In vitro , EpCAM enhanced cancer cell stemness, as reflected by increased abilities of proliferation, self-renewal, migration and invasion, which was counteracted by arenobufagin. Furthermore, arenobufagin inhibited the viability of Hep3B and Huh7 cells with IC 50 values of 36.4 nM and 123.4 nM after 72 h of treatment, respectively. Molecular docking data further indicated that arenobufagin binds EpCAM. Moreover, arenobufagin inhibited early progression of HCC through EpCAM in a zebrafish xenograft tumor model mimicking early-stage hepatocellular carcinoma without blood vessels in vivo . This study supports a tumor-promoting role of EpCAM in early-stage hepatocellular carcinoma by facilitating cancer stemness and suggests that arenobufagin might be promising candidate for EpCAM inhibition.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2024-0064 |
| spellingShingle | Lijuan Deng Lifang Zou Chunhong Zhou Fuqin Yang Fen Ouyang Yingru Zhu Huihui Cao Min Hu Xiaoshen Zhang Junshan Liu Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness Acta Materia Medica |
| title | Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness |
| title_full | Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness |
| title_fullStr | Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness |
| title_full_unstemmed | Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness |
| title_short | Arenobufagin suppresses the progression of early-stage hepatocellular carcinoma by inhibiting EpCAM-mediated tumor stemness |
| title_sort | arenobufagin suppresses the progression of early stage hepatocellular carcinoma by inhibiting epcam mediated tumor stemness |
| url | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2024-0064 |
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