Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis I

Tumors occasionally express oncogenes via aberrant activation of transposable elements (TE), but a role for this process in oncogenesis was seldom demonstrated. Here, we identify expression of the hominid-restricted retrogene POU5F1B through aberrant activation of an endogenous retroviral promoter as a strong negative prognostic marker in colorectal cancer (CRC). We further determine that POU5F1B is membrane-enriched and interacts with ERBB2 and associated effectors, and fosters the proliferation and metastatic potential of CRC cells through intracellular signaling events and release of trans-acting molecules involved in cell growth, angiogenesis and cell adhesion. As POU5F1B is apparently non-essential and only lowly expressed in normal tissues, and as POU5F1B-containing TE-driven transcripts are detected in other tumors besides CRC, these data provide interesting leads for the development of cancer therapies. Overall design: RNA-sequencing analysis of POU5F1B- and GFP-overexpressing SW480 cells.

肿瘤偶尔会通过转座因子（transposable elements, TE）的异常激活表达癌基因，但该过程在肿瘤发生中的作用却鲜有研究证实。本研究鉴定出，人科特异性逆转录基因POU5F1B可通过内源性逆转录病毒启动子的异常激活得以表达，且其表达水平可作为结直肠癌（colorectal cancer, CRC）的强阴性预后标志物。本研究进一步证实，POU5F1B具有膜富集特性，可与ERBB2及其相关效应分子相互作用，并通过细胞内信号传导事件以及释放参与细胞生长、血管生成与细胞黏附的反式作用分子，增强结直肠癌细胞的增殖能力与转移潜能。鉴于POU5F1B显然为非必需基因，且仅在正常组织中呈低水平表达，同时在结直肠癌以外的其他多种肿瘤中均可检测到携带POU5F1B的转座因子驱动转录本，本研究数据为癌症治疗策略的开发提供了颇具价值的研究线索。实验设计概况：对过表达POU5F1B与绿色荧光蛋白（green fluorescent protein, GFP）的SW480细胞开展RNA测序分析。