• 纳入301例大肠腺瘤或腺癌患者(SYSCOL队列),分析癌症特异性转座因子驱动的转座嵌合基因转录本(TcGTs);
  • 灵长类特异性内源性逆转录病毒启动子LTR66的异常激活驱动人源性限制性反转录基因POU5F1B的表达,LTR66-POU5F1B是CRC预后不良的标志物(仅限SYSCOL);
  • POU5F1B促进CRC细胞的增殖和转移潜能;
  • POU5F1B是膜富集蛋白,与蛋白激酶、细胞骨架相关分子等结合,诱导细胞内信号事件和与细胞生长和细胞粘附相关的反式作用因子的释放。
Nature Communications近期发表的文章,转座子激活基因——POU5F1B能促进结直肠癌的增殖和转移潜能,与CRC的不良预后相关。并且,POU5F1B是一种仅在正常组织中低表达的非必需基因,而含POU5F1B的TcGTs在CRC及其他肿瘤中都检测到,或可成为癌症治疗的潜在靶点。

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis



2022-08-20, Article

Abstract & Authors:展开

The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we find that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic biomarker. Correlating this observation, we demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determine that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.

First Authors:
Laia Simó-Riudalbas

Correspondence Authors:
Laia Simó-Riudalbas,Didier Trono

All Authors:
Laia Simó-Riudalbas,Sandra Offner,Evarist Planet,Julien Duc,Laurence Abrami,Sagane Dind,Alexandre Coudray,Mairene Coto-Llerena,Caner Ercan,Salvatore Piscuoglio,Claus Lindbjerg Andersen,Jesper Bertram Bramsen,Didier Trono