Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose-6-phosphate isomerase, and phosphoglycerate kinase 1, while circ-CUX1 binds to EWS RNA-binding protein 1 (EWSR1) to facilitate its interaction with MYC-associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression.
These findings help to define the molecular mechanism driving the high expression of PPARgamma1 in breast cancer and raise new questions regarding the role of MAZ in cancer progression.
Altered Prox1 mRNA expression is partly regulated by MAZ, and mutation of the prospero domain in HCC indicates an involvement for Prox1 during tumor progression.