Soen Bieke, Vandamme Niels, Berx Geert, Schwaller Jürg, Van Vlierberghe Pieter, Goossens Steven
Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Cancer Research Institute Ghent, Ghent, Belgium.
Hemasphere. 2018 May 11;2(3):e43. doi: 10.1097/HS9.0000000000000043. eCollection 2018 Jun.
ZEB1 and ZEB2 play pivotal roles in solid cancer metastasis by allowing cancer cells to invade and disseminate through the transcriptional regulation of epithelial-to-mesenchymal transition. ZEB expression is also associated with the acquisition of cancer stem cell properties and therapy resistance. Consequently, expression levels of ZEB1/2 and of their direct target genes are widely seen as reliable prognostic markers for solid tumor aggressiveness and cancer patient outcome. Recent loss-of-function mouse models demonstrated that both ZEBs are also essential hematopoietic transcription factors governing blood lineage commitment and fidelity. Interestingly, both gain- and loss-of-function mutations have been reported in multiple hematological malignancies. Combined with emerging functional studies, these data suggest that ZEB1 and ZEB2 can act as tumor suppressors and/or oncogenes in blood borne malignancies, depending on the cellular context. Here, we review these novel insights and discuss how balanced expression of ZEB proteins may be essential to safeguard the functionality of the immune system and prevent leukemia.
ZEB1和ZEB2通过上皮-间质转化的转录调控使癌细胞得以侵袭和播散，在实体癌转移中发挥关键作用。ZEB表达还与癌症干细胞特性的获得及治疗抗性相关。因此，ZEB1/2及其直接靶基因的表达水平被广泛视为实体瘤侵袭性和癌症患者预后的可靠预后标志物。最近的功能缺失小鼠模型表明，这两种ZEB蛋白也是控制血液谱系定向分化和稳定性的重要造血转录因子。有趣的是，在多种血液系统恶性肿瘤中均报道了功能获得性和功能缺失性突变。结合新出现的功能研究，这些数据表明，根据细胞环境，ZEB1和ZEB2在血源性恶性肿瘤中可作为肿瘤抑制因子和/或癌基因。在此，我们综述这些新见解，并讨论ZEB蛋白的平衡表达对于维护免疫系统功能和预防白血病可能如何至关重要。
