UBE2C mediates follicular thyroid carcinoma invasion and metastasis via K29-Specific vimentin ubiquitination

被引:0
|
作者
Xu, Lei [1 ,2 ]
Dai, Bao [2 ]
Zhang, Lingyun [2 ]
Chen, Weijian [2 ]
Rong, Shikuo [1 ]
Chen, Jianghong [2 ]
Song, Muye [3 ]
Lan, Ziteng [2 ]
Liu, Yongchen [2 ]
Wang, Linhe [2 ]
Li, Jinghua [4 ]
Chen, Jian [2 ]
Wu, Zeyu [1 ,2 ]
机构
[1] Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Guangdong Cardiovasc Inst, Guangzhou 510080, Guangdong, Peoples R China
[2] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Thyroid & Hernia Surg, Guangzhou 510080, Guangdong, Peoples R China
[3] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Anesthesiol, Guangzhou 510080, Guangdong, Peoples R China
[4] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Lab, 106 Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China
关键词
Follicular thyroid carcinoma; Ubiquitin-proteasome system; Epithelial-mesenchymal transition; Prognostic biomarker; RESISTANT PROSTATE-CANCER;
D O I
10.1016/j.canlet.2025.217624
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Follicular thyroid carcinoma (FTC) poses significant clinical challenges due to its vascular invasion tendency and distant metastasis potential, leading to poorer patient outcomes compared to other thyroid carcinomas. Although ubiquitin-conjugating enzyme E2C (UBE2C) has been widely studied in various cancers, its specific role in FTC progression remains insufficiently explored. This study demonstrates UBE2C's dual functionality in FTC through clinical analysis and experimental validation. Single-cell RNA sequencing of FTC specimens revealed marked UBE2C upregulation associated with aggressive tumor behavior and unfavorable prognosis. Functional studies showed that UBE2C overexpression paradoxically enhanced cellular proliferation while suppressing migration and invasion through EMT modulation. Mechanistic investigations identified vimentin as a key substrate, where UBE2C mediated K29-linked ubiquitination leading to its degradation. Animal models yielded unexpected findings where UBE2C knockdown reduced primary tumor growth but promoted metastasis, validating its context-dependent roles. These results establish UBE2C as a molecular regulator balancing proliferation and invasion in FTC through post-translational modification of cytoskeletal components, suggesting its therapeutic potential for targeted intervention strategies.
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页数:14
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