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

The transcription factor CCAAT/enhancer-binding protein alpha (C/EBP alpha) 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 similar to 10% of acute myeloid leukemia (AML), stablishing a tumor suppressor role for C/EBP alpha. Deregulation of C/EBP alpha 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/EBP alpha function in non-hematopoietic tissues is regulated by alternative mechanisms. Here we review the function of C/EBP alpha in solid tumors and focus on the molecular mechanisms underlying its tumor suppressive role.