The role of IRES trans-acting factors in carcinogenesis

•ITRES-transacting factors (ITAFs) are proteins that regulate IRES-translation.•Expression of ITAFs is frequently misregulated in cancer.•ITAFs control expression of proteins involved in key aspects of carcinogenesis.•Targeting ITAFs represent novel therapeutic approaches to fight cancer.

Regulation of protein expression through RNA metabolism is a key aspect of cellular homeostasis. Upon specific cellular stresses, distinct transcripts are selectively controlled to modify protein output in order to quickly and appropriately respond to stress. Reprogramming of the translation machinery is one node of this strict control that typically consists of an attenuation of the global, cap-dependent translation and accompanying switch to alternative mechanisms of translation initiation, such as internal ribosome entry site (IRES)-mediated initiation. In cancer, many aspects of the RNA metabolism are frequently misregulated to provide cancer cells with a growth and survival advantage. This includes changes in the expression and function of RNA binding proteins termed IRES trans-acting factors (ITAFs) that are central to IRES translation. In this review, we will examine select emerging, as well as established, ITAFs with important roles in cancer initiation and progression, and in particular their role in IRES-mediated translation. This article is part of a Special Issue entitled: Translation and Cancer.