Oncogenic role of a developmentally regulated NTRK2 splice variant.
Oncogenic role of a developmentally regulated NTRK2 splice variant.
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DOI：
10.1126/sciadv.abo6789
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发表时间：
2022-10-07
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
时间调节的选择性剪接对正常发育至关重要，但错误的剪接选择可能是有害的。在这里，我们强调了神经营养因子受体剪接变体TrkB.T1在人类和小鼠多种肿瘤类型的神经发育，胚胎发生，转化和肿瘤发生中的先前未识别的作用。TrkB.T1是胚胎器官发生中主要的NTRK 2亚型，这种胚胎模式的强制过表达在肿瘤抑制因子丧失的背景下导致小鼠中的多种实体瘤和非实体瘤。TrkB.T1也作为主要的NTRK同种型出现在广泛的成人和儿童肿瘤中，包括那些携带原肌球蛋白受体激酶融合的肿瘤。亲和纯化-质谱蛋白质组学分析揭示了与已知发育和致癌信号传导途径（如Wnt、转化生长因子-β、Sonic Hedgehog和Ras）的不同相互作用物。从剪接因子的改变到基因表达的变化，发现具有胚胎祖先的同种型特异性癌基因有可能塑造我们对发育系统和肿瘤学的看法。TrkB.T1在出生后在许多细胞类型中过表达时是致癌的，这些细胞类型在正常胚胎发育期间曾经表达过它。
Temporally regulated alternative splicing choices are vital for proper development, yet the wrong splice choice may be detrimental. Here, we highlight a previously unidentified role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis across multiple tumor types in humans and mice. TrkB.T1 is the predominant NTRK2 isoform across embryonic organogenesis, and forced overexpression of this embryonic pattern causes multiple solid and nonsolid tumors in mice in the context of tumor suppressor loss. TrkB.T1 also emerges as the predominant NTRK isoform expressed in a wide range of adult and pediatric tumors, including those harboring tropomyosin receptor kinase fusions. Affinity purification–mass spectrometry proteomic analysis reveals distinct interactors with known developmental and oncogenic signaling pathways such as Wnt, transforming growth factor–β, Sonic Hedgehog, and Ras. From alterations in splicing factors to changes in gene expression, the discovery of isoform specific oncogenes with embryonic ancestry has the potential to shape the way we think about developmental systems and oncology. TrkB.T1 is oncogenic when overexpressed postnatally in many cell types that once expressed it during normal embryonic development.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
4.3
作者：
Akil, Hussein;Perraud, Aurelie;Mathonnet, Muriel
通讯作者：
Mathonnet, Muriel
影响因子：
45.3
作者：
Eggert, A;Grotzer, MA;Evans, AE
通讯作者：
Evans, AE