VGLL4 is a transcriptional cofactor acting as a novel tumor suppressor via interacting with TEADs.

Vestigial Like Family Member 4 (VGLL4) is a transcriptional cofactor of VGLL family, which includes VGLL1-4. Unlike other members of VGLL family, VGLL4 was described as a novel tumor suppressor containing two TDU motifs. VGLL4 executes its biological function through two TDU domains via interacting with TEA domain (TEAD) transcription factors. Lower expression of VGLL4 usually indicates poor survival in many cancers, such as lung cancer, gastric cancer, breast cancer, colorectal cancer, bladder cancer, pancreatic adenocarcinoma and esophageal squamous cancer. In cancer cells, the expression of VGLL4 is lower than that of normal tissues, moreover, expression level of VGLL4 is positively related to survival rate. VGLL4 is found to play an important role in several signal pathways, mainly acts as a tumor suppressor interacting with TEADs. In Hippo signaling pathway, VGLL4 competes with YAP in binding to TEADs and inhibits the downstream of YAP. In Wnt/β-catenin signaling pathway, VGLL4 negatively regulates Wnt/β-catenin signaling pathway via inhibiting β-catenin and TCF (T-cell factor). VGLL4 can also suppress epithelial-mesenchymal transition (EMT) and contribute to apoptosis signaling pathway.