HOX genes and the NF-κB pathway: A convergence of developmental biology, inflammation and cancer biology

The roles of HOX transcription factors as oncogenes and tumor suppressor genes, and the NF-KB pathway in chronic inflammation, both leading to cancer are well-established. HOX transcription factors are members of an evolutionarily conserved family of proteins required for anteroposterior body axis patterning during embryonic development, and are often dysregulated in cancer. The NF-KB pathway aids inflammation and immunity but it is also important during embryonic development. It is frequently activated in both solid and hematological malignancies. NF-KB and HOX proteins can influence each other through mutual transcriptional regulation, protein-protein interactions, and regulation of upstream and downstream interactors. These interactions have important implications both in homeostasis and in disease. In this review, we summarize the role of HOX proteins in regulating inflammation in homeostasis and disease- with a particular emphasis on cancer. We also describe the relationship between HOX genes and the NF-KB pathway, and discuss potential therapeutic strategies.