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.

在缺乏早期诊断的情况下，结直肠癌 (CRC) 的治疗是一项未满足的医疗需求。在这里，在表征 SYSCOL 队列中该肿瘤产生的癌症特异性转座因子驱动的转嵌合基因转录物 (TcGTs) 后，我们发现原始人限制性逆转录基因 POU5F1B的表达通过异常激活灵长类动物特异性内源性逆转录病毒启动子是一种强烈的阴性预后生物标志物。与这一观察结果相关，我们证明 POU5F1B 促进 CRC 细胞的增殖和转移潜力。我们进一步确定，尽管 POU5F1B 与 POU5F1/OCT4 转录因子存在系统发育关系，但它是一种富膜蛋白，与蛋白激酶和已知靶标或相互作用物以及细胞骨架相关分子相关，并诱导细胞内信号传导事件以及参与细胞生长和细胞粘附的反式作用因子的释放。由于POU5F1B显然是非必需基因，仅在正常组织中低表达，而POU5F1B在除 CRC 之外的其他肿瘤中检测到含有 TcGT，我们的数据为癌症疗法的开发提供了有趣的线索。