Lourenço A R, Coffer P J
Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Oncogene. 2017 Sep 14;36(37):5221-5230. doi: 10.1038/onc.2017.151. Epub 2017 May 15.
The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) plays a critical role during embryogenesis and is thereafter required for homeostatic glucose metabolism, adipogenesis and myeloid development. Its ability to regulate the expression of lineage-specific genes and induce growth arrest contributes to the terminal differentiation of several cell types, including hepatocytes, adipocytes and granulocytes. CEBPA loss of-function mutations contribute to the development of ~10% of acute myeloid leukemia (AML), stablishing a tumor suppressor role for C/EBPα. Deregulation of C/EBPα expression has also been reported in a variety of additional human neoplasias, including liver, breast and lung cancer. However, functional CEBPA mutations have not been found in solid tumors, suggesting that abrogation of C/EBPα function in non-hematopoietic tissues is regulated by alternative mechanisms. Here we review the function of C/EBPα in solid tumors and focus on the molecular mechanisms underlying its tumor suppressive role.
转录因子CCAAT/增强子结合蛋白α（C/EBPα）在胚胎发育过程中发挥关键作用，并且在维持葡萄糖代谢稳态、脂肪生成和髓系发育中是必需的。它调节谱系特异性基因表达并诱导生长停滞的能力有助于包括肝细胞、脂肪细胞和粒细胞在内的几种细胞类型的终末分化。CEBPA功能丧失突变导致约10%的急性髓系白血病（AML）发生，确立了C/EBPα的肿瘤抑制作用。在包括肝癌、乳腺癌和肺癌在内的多种其他人类肿瘤中也报道了C/EBPα表达失调。然而，在实体瘤中尚未发现功能性CEBPA突变，这表明非造血组织中C/EBPα功能的丧失是由其他机制调节的。在此，我们综述C/EBPα在实体瘤中的功能，并聚焦于其肿瘤抑制作用的分子机制。
