CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

CUT-like homeobox 1 (CUX1) is a homeobox gene that is implicated in both tumour suppression and progression. The accumulated evidence supports a model of haploinsufficiency whereby reduced CUX1 expression promotes tumour development. Paradoxically, increased CUX1 expression is associated with tumour progression, and ectopic CUX1 expression in transgenic mice increases tumour burden in several tissues. One CUX1 isoform functions as an ancillary factor in base excision repair and the other CUX1 isoforms act as transcriptional activators or repressors. Several transcriptional targets and cellular functions of CUX1 affect tumorigenesis; however, we have yet to develop a mechanistic framework to reconcile the opposite roles of CUX1 in cancer protection and progression.