A tumor suppressor role for C/EBPα in solid tumors: more than fat and blood?


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 discuss the function of C/EBPα in solid tumors, focussing on the molecular mechanisms underlying its tumor suppressive role. This review was recently published in Oncogene