| 题名 | Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis |
| 作者 | |
| 通讯作者 | Guan，Haixia; Rao，Feng; Zhao，Li |
| 发表日期 | 2024-05-15
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| DOI | |
| 发表期刊 | |
| EISSN | 2041-1723
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| 卷号 | 15期号:1 |
| 摘要 | MAPK pathway-driven tumorigenesis, often induced by BRAF, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAF-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAF signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation. |
| 相关链接 | [Scopus记录] |
| 收录类别 | |
| 语种 | 英语
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| 学校署名 | 通讯
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| Scopus记录号 | 2-s2.0-85193372587
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| 来源库 | Scopus
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| 引用统计 |
被引频次[WOS]：2
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| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/760925 |
| 专题 | 生命科学学院 |
| 作者单位 | 1.Department of Thyroid and Neck Oncology,Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,National Clinical Research Center for Cancer,The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics,Key Laboratory of Immune Microenvironment and Disease 2.Department of Endocrinology,Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,Guangdong,China 3.Department of Pathology,Tianjin Central Hospital of Gynecology and Obstetrics,Tianjin,China 4.School of Life Sciences,Southern University of Science and Technology,Shenzhen,Guangdong,China 5.Department of General Surgery,Tianjin Medical University General Hospital,Tianjin Medical University,Tianjin,China 6.Department of Radiation Oncology,Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,National Clinical Research Center for Cancer,Tianjin Medical University Cancer Institute and Hospital,Tianjin,China 7.Department of Thyroid and Neck Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,Tianjin,China |
| 通讯作者单位 | 生命科学学院 |
| 推荐引用方式 GB/T 7714 |
Zhang，Zhenlei,Wu，Yufan,Fu，Jinrong,et al. Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis[J]. Nature Communications,2024,15(1).
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| APA |
Zhang，Zhenlei.,Wu，Yufan.,Fu，Jinrong.,Yu，Xiujie.,Su，Yang.,...&Zhao，Li.(2024).Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis.Nature Communications,15(1).
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| MLA |
Zhang，Zhenlei,et al."Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis".Nature Communications 15.1(2024).
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| 条目包含的文件 | 条目无相关文件。 | |||||
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