Molecular Responses to Hypoxia-Inducible Factor 1α and Beyond

Cellular response to changes in oxygen tension during normal development or pathologic processes is, in part, regulated by hypoxia-inducible factor (HIF), an oxygen-sensitive transcription factor. HIF activity is primarily controlled through post-translational modifications and stabilization of HIF-1 alpha and HIF-2 alpha proteins and is regulated by a number of cellular pathways involving both oxygen-dependent and -independent mechanisms. Stabilization of HIF-1 alpha activates transcription of genes that participate in key pathways in carcinogenesis, such as angiogenesis, dedifferentiation, and invasion. Since its discovery more than two decades ago, HIF-1 alpha has become a hot topic in molecular research and has been implicated not only in disease pathology but also in prognosis. In this review, we will focus on recent insights into HIF-1 alpha regulation, function, and gene expression. We will also discuss emerging data on the involvement of HIF in cancer prognosis and therapeutic interventions.