CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling
Abstract CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07470-x |
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| _version_ | 1850252406708764672 |
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| author | Bing Yan QiuYu Lu TianMing Gao KunQing Xiao QianNi Zong HongWei Lv GuiShuai Lv Liang Wang ChunYing Liu Wen Yang GuoQing Jiang |
| author_facet | Bing Yan QiuYu Lu TianMing Gao KunQing Xiao QianNi Zong HongWei Lv GuiShuai Lv Liang Wang ChunYing Liu Wen Yang GuoQing Jiang |
| author_sort | Bing Yan |
| collection | DOAJ |
| description | Abstract CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly expressed in liver CSCs. CD146 overexpression promoted the self-renewal ability and chemoresistance of Hepatocellular Carcinoma (HCC) cells in vitro and tumorigenicity in vivo. Inversely, knockdown of CD146 restrained these abilities. Mechanistically, CD146 activated the NF-κB signaling to up-regulate JAG2 expression and activated the Notch signaling, which resulted in increased stemness of HCC. Furthermore, JAG2 overexpression restored the Notch signaling activity, the stemness, and chemotherapeutic resistance caused by CD146 knockdown. These results demonstrated that CD146 positively regulates HCC stemness by activating the JAG2-NOTCH signaling. Combined targeting of CD146 and JAG2 may represent a novel therapeutic strategy for HCC treatment. |
| format | Article |
| id | doaj-art-6ed08fe1a19345288c3b3dc4c1d4a2f7 |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-6ed08fe1a19345288c3b3dc4c1d4a2f72025-08-20T01:57:40ZengNature Publishing GroupCell Death and Disease2041-48892025-03-0116111210.1038/s41419-025-07470-xCD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signalingBing Yan0QiuYu Lu1TianMing Gao2KunQing Xiao3QianNi Zong4HongWei Lv5GuiShuai Lv6Liang Wang7ChunYing Liu8Wen Yang9GuoQing Jiang10Department of Hepatobiliary Surgery, Northern Jiangsu People’s HospitalInternational Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)Department of Hepatobiliary Surgery, Northern Jiangsu People’s HospitalDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s HospitalInternational Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Naval Medical University (Second Military Medical University)Department of Hepatobiliary Surgery, Northern Jiangsu People’s HospitalAbstract CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly expressed in liver CSCs. CD146 overexpression promoted the self-renewal ability and chemoresistance of Hepatocellular Carcinoma (HCC) cells in vitro and tumorigenicity in vivo. Inversely, knockdown of CD146 restrained these abilities. Mechanistically, CD146 activated the NF-κB signaling to up-regulate JAG2 expression and activated the Notch signaling, which resulted in increased stemness of HCC. Furthermore, JAG2 overexpression restored the Notch signaling activity, the stemness, and chemotherapeutic resistance caused by CD146 knockdown. These results demonstrated that CD146 positively regulates HCC stemness by activating the JAG2-NOTCH signaling. Combined targeting of CD146 and JAG2 may represent a novel therapeutic strategy for HCC treatment.https://doi.org/10.1038/s41419-025-07470-x |
| spellingShingle | Bing Yan QiuYu Lu TianMing Gao KunQing Xiao QianNi Zong HongWei Lv GuiShuai Lv Liang Wang ChunYing Liu Wen Yang GuoQing Jiang CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling Cell Death and Disease |
| title | CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling |
| title_full | CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling |
| title_fullStr | CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling |
| title_full_unstemmed | CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling |
| title_short | CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling |
| title_sort | cd146 regulates the stemness and chemoresistance of hepatocellular carcinoma via jag2 notch signaling |
| url | https://doi.org/10.1038/s41419-025-07470-x |
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