NKX2-1
小结
NKX2-1编码蛋白是一种含有同源框的转录因子，参与肺、甲状腺和前脑腹侧的发育。NKX2-1的表达仅限于这些谱系中的特定细胞类型，并且NKX2-1在调节细胞类型特异性转录程序中具有作用。在肺中，NKX2-1是表面活性剂表达的关键调节因子，表面活性物质是降低肺部表面张力的重要蛋白质，在宿主防御感染和炎症中发挥关键作用。甲状腺前体细胞表达NKX2-1以调节甲状腺特异性基因，并且NKX2-1表达的维持在成体组织中对于调节甲状腺激素是重要的。在甲状腺癌中，NKX2-1主要在滤泡性肿瘤和乳头状癌中表达，而在间变性癌中不表达。NKX2-1的胚系突变在多结节甲状腺肿和乳头状甲状腺癌的家系中被鉴定。在肺腺癌中，NKX2-1的体细胞突变是罕见的，但NKX2-1的持续表达往往与基因扩增有关。最近，NKX2-1与T细胞受体或免疫球蛋白重链基因座的重排也在T细胞急性淋巴细胞白血病中被发现。因此，NKX2-1在不同癌症类型的肿瘤进展中发挥背景特异性作用。
NKX2-1 is a homeobox-containing transcription factor essential for the development of the lung, thyroid and ventral forebrain. Expression of NKX2-1 is restricted to specific cell types in these lineages and NKX2-1 has a role in the regulation of cell-type specific transcriptional programs. In the lung, NKX2-1 is a critical regulator of the expression of surfactants, which are proteins important for reducing surface tension in the lung and play a critical role in host defense against infection and inflammation. Thyroid precursor cells express NKX2-1 in order to regulate thyroid-specific genes and maintenance of NKX2-1 expression is important in adult tissues for the regulation of thyroid hormones. In thyroid carcinomas, NKX2-1 is primarily expressed in follicular neoplasm and papillary carcinoma but not in anaplastic carcinoma. Germline mutations in NKX2-1 have been identified in families affected by multinodular goiter and papillary thyroid carcinoma. In lung adenocarcinoma, somatic mutations of NKX2-1 are rare but sustained expression of NKX2-1 is frequently associated with gene amplification. However, loss of NKX2-1 expression is also associated with favorable prognosis and reduced metastasis in murine models and humans, likely due to altered differentiation programs controlled by NKX2-1. Rearrangements of NKX2-1 with T-cell receptor or immunoglobulin heavy chain loci were also recently identified in T-cell acute lymphoblastic leukemia. Therefore, NKX2-1 plays context-specific roles in tumor progression in different cancer types.