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素-C在甲状腺癌中增强了Wnt信号传递
Heather A Hartmann1, Matthew A Loberg1, George J Xu1
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
bioRxiv : the preprint server for biology
|November 22, 2024
概括
泰纳辛-C (TNC) 通过增强Wnt信号传输,入侵和转移来促进对抗性甲状腺癌 (ATC). 针对TNC可能为这种侵略性癌症提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞外矩阵生物学 细胞外矩阵生物学
背景情况:
- 素-C (TNC) 是一种涉及发育和疾病的细胞外基质蛋白.
- 在发育和癌症,包括侵袭性甲状腺癌中,Wnt信号是至关重要的.
- 高TNC和Wnt信号被观察到在厌塑性甲状腺癌 (ATC).
研究的目的:
- 调查Tenascin-C (TNC) 在促进甲状腺癌中依赖带的Wnt信号传递中的作用.
- 确定TNC对甲状腺癌进展,入侵和转移的贡献.
主要方法:
- 在三个独立的甲状腺癌患者队列中进行大量RNA测序.
- 在患者瘤中用于TNC的空间定位的RNA in situ杂交.
- 在体外Wnt记者测定和在体内研究中使用ATC小鼠异种移植模型.
主要成果:
- TNC表达与侵袭性甲状腺癌的特征相关,如形组织学,甲状腺外延伸和转移.
- 在癌细胞中,TNC在侵袭边缘和血管内侵袭区域的上调.
- 在体外,TNC 结合 Wnt 配体并增强 Wnt 信号传递.
- 在体内,TNC在ATC小鼠模型中增强了Wnt信号传输,瘤负担,入侵和转移.
结论:
- 素-C (TNC) 增强了Wnt信号传递,驱动癌细胞入侵和甲状腺癌转移.
- TNC与Wnt配体的相互作用为新型甲状腺癌生物标志物和治疗药物提供了潜在的标.
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