Cerveira Nuno, Santos Joana, Teixeira Manuel R
Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
Crit Rev Oncog. 2009;15(1-2):91-115. doi: 10.1615/critrevoncog.v15.i1-2.40.
Septins are an evolutionarily conserved family of GTP-binding proteins that associate with cellular membranes and the actin and microtubule cytoskeletons. Fourteen septin genes have been characterized to date (SEPT1 to SEPT14) in humans. Septins have been reported to be misregulated in various human diseases, including neurological disorders, infection, and neoplasia. In this review, we describe what is known thus far about septin deregulation in myeloid neoplasia. Septin abnormalities in myeloid neoplasia can be divided into two major groups. First, some septins (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been repeatedly identified as in-frame fusion partners of the MLL gene in de novo and therapy-related myeloid neoplasia, in both children and adults. Second, deregulation of the expression of septin family genes in hematological cancers can be observed either with or without the concomitant presence of MLL gene fusions. Although current hypotheses regarding the roles of septins in oncogenesis remain speculative for the most part, the fundamental roles of septins in cytokinesis, membrane remodeling, and compartmentalization can provide some clues on how abnormalities in the septin cytoskeleton could be involved in neo-plastic disorders.
Septins是一类进化上保守的GTP结合蛋白家族，与细胞膜以及肌动蛋白和微管细胞骨架相关联。迄今为止，已在人类中鉴定出14个septin基因（SEPT1至SEPT14）。据报道，Septins在包括神经疾病、感染和肿瘤形成在内的各种人类疾病中存在调控异常。在本综述中，我们描述了目前关于髓系肿瘤中septin失调的已知情况。髓系肿瘤中的septin异常可分为两大类。第一，在儿童和成人的原发性和治疗相关髓系肿瘤中，一些septin（SEPT2、SEPT5、SEPT6、SEPT9和SEPT11）已被反复鉴定为MLL基因的框内融合伴侣。第二，在血液系统癌症中，无论是否同时存在MLL基因融合，均可观察到septin家族基因表达的失调。尽管目前关于septin在肿瘤发生中作用的假说在很大程度上仍属推测，但septin在胞质分裂、膜重塑和区室化中的基本作用可为septin细胞骨架异常如何参与肿瘤性疾病提供一些线索。
