Targeted degradation of GOLM1 by CC-885 via CRL4-CRBN E3 ligase inhibits hepatocellular carcinoma progression
文献类型：期刊论文
| 作者 | He, Jingliang6; Guo, Jingli5,6,7; Liu, Shunfang3,6; Li, Hanxue6; Ma, Yuanyuan1,4; Ma, Shaojie6; Hu, Zhongke6; Zhao, Wensi2; Tan, Minjia5,7 ; Liu, Wei1,4
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| 刊名 | CELLULAR SIGNALLING
 |
| 出版日期 | 2025-06-01 |
| 卷号 | 130页码:15 |
| 关键词 | Hepatocellular carcinoma CC-885 GOLM1 Ubiquitination Apoptosis CRBN |
| ISSN号 | 0898-6568 |
| DOI | 10.1016/j.cellsig.2025.111665 |
| 英文摘要 | Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, emphasizing the urgent need for novel therapeutic strategies. In this study, we investigate the anti-tumor potential of CC-885, a cereblon (CRBN) modulator known for its efficacy in targeting neoplastic cells through proteasomal degradation pathways. Our findings demonstrate that CC-885 exhibits potent anti-tumor activity against HCC. In vitro assays revealed that CC-885 significantly inhibits the proliferation, migration, and invasion of HCC cells. These effects were corroborated in vivo, where CC-885 markedly suppressed tumor growth and angiogenesis in chick embryos and impeded the progression of orthotopic liver tumors in murine models. Mechanistically, CC-885 selectively reduces GOLM1 protein levels via ubiquitin-mediated proteasomal degradation. Knockdown of GOLM1 recapitulated the anti-proliferative effects of CC-885, while overexpression of GOLM1 conferred resistance to CC-885induced apoptosis and growth inhibition. Further investigation revealed that CC-885 facilitates the interaction between GOLM1 and the E3 ubiquitin ligase CRBN, promoting the ubiquitination and subsequent degradation of GOLM1. Transcriptomic analyses showed that both CC-885 treatment and GOLM1 knockdown modulate critical pathways involved in apoptosis. These findings position CC-885 as a promising therapeutic candidate for HCC, acting primarily through CRBN-dependent degradation of GOLM1, and support its further development for clinical application. |
| WOS关键词 | IMID RESISTANCE ; CANCER ; CRBN ; UBIQUITINATION ; BIOMARKER |
| 资助项目 | Key Program of Basic Science (Natural Science) of Jiangsu Province[22KJA350001] ; Huaguo Mountain Talent Plan of Lianyungang City (Innovative Talents Liu Bin) ; Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province[CXPJJH123003-027] ; Scientific Research Foundation for Returned Scholars of Tongji Hospital[2022hgry021] ; Scientific Research Fund of Tongji Hospital[2023A09] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001436733000001 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316460]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Wei; Liu, Bin |
| 作者单位 | 1.Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA 2.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai 200433, Peoples R China 3.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Oncol, Jiefang Rd 1095, Wuhan 430030, Hubei, Peoples R China 4.Med Coll Wisconsin, Canc Ctr, Milwaukee, WI 53226 USA 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Jiangsu Ocean Univ, Coll Pharm, Jiangsu Key Lab Marine Pharmaceut Cpds Screening, Lianyungang 222005, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Jingliang,Guo, Jingli,Liu, Shunfang,et al. Targeted degradation of GOLM1 by CC-885 via CRL4-CRBN E3 ligase inhibits hepatocellular carcinoma progression[J]. CELLULAR SIGNALLING,2025,130:15. |
| APA | He, Jingliang.,Guo, Jingli.,Liu, Shunfang.,Li, Hanxue.,Ma, Yuanyuan.,...&Liu, Bin.(2025).Targeted degradation of GOLM1 by CC-885 via CRL4-CRBN E3 ligase inhibits hepatocellular carcinoma progression.CELLULAR SIGNALLING,130,15. |
| MLA | He, Jingliang,et al."Targeted degradation of GOLM1 by CC-885 via CRL4-CRBN E3 ligase inhibits hepatocellular carcinoma progression".CELLULAR SIGNALLING 130(2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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