biostudies-literatureGuo YProgram for Professor of Special Appointment (Young Eastern Scholar) at Shanghai Institutions of Higher Learning (to C-Y. L.).National Natural Science Foundation of China4995https://www.ebi.ac.uk/biostudies/studies/S-EPMC9411202biostudies-literatureUnknown13(1)Dysregulation of Hippo pathway leads to hyperactivation of YAP-TEAD transcriptional complex in various cancers, including colorectal cancer (CRC). In this study, we observed that HHEX (Hematopoietically expressed homeobox) may enhance transcription activity of the YAP-TEAD complex. HHEX associates with and stabilizes the YAP-TEAD complex on the regulatory genomic loci to coregulate the expression of a group of YAP/TEAD target genes. Also, HHEX may indirectly regulate these target genes by controlling YAP/TAZ expression. Importantly, HHEX is required for the pro-tumorigenic effects of YAP during CRC progression. In response to serum stimulation, CK2 (Casein Kinase 2) phosphorylates HHEX and enhances its interaction with TEAD4. A CK2 inhibitor CX-4945 diminishes the interaction between HHEX Nature communicationsCK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis.PMC941120281874177819740608187354782073056Du PLiu CYZhu ZGuo YHuang ZCui LYu WHong WZhou ZfalseCK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis.Dysregulation of Hippo pathway leads to hyperactivation of YAP-TEAD transcriptional complex in various cancers, including colorectal cancer (CRC). In this study, we observed that HHEX (Hematopoietically expressed homeobox) may enhance transcription activity of the YAP-TEAD complex. HHEX associates with and stabilizes the YAP-TEAD complex on the regulatory genomic loci to coregulate the expression of a group of YAP/TEAD target genes. Also, HHEX may indirectly regulate these target genes by controlling YAP/TAZ expression. Importantly, HHEX is required for the pro-tumorigenic effects of YAP during CRC progression. In response to serum stimulation, CK2 (Casein Kinase 2) phosphorylates HHEX and enhances its interaction with TEAD4. A CK2 inhibitor CX-4945 diminishes the interaction between HHEX 2022-01-01T00:00:00Z2022 Aug2026-05-28T01:11:47.488Z2025-04-19T22:49:19.701ZS-EPMC94112023600841110.1038/s41467-022-32674-6