Multiple Roles of Vestigial-Like Family Members in Tumor Development

Vestigial-like family (VGLL) members are mammalian orthologs of vestigial gene in Drosophila, and they consist of four homologs (VGLL1-4). VGLL members have TDU motifs that are binding regions to TEA/ATSS-DNA-binding domain transcription factor (TEAD). Through TDU motifs, VGLL members act as transcriptional cofactors for TEAD. VGLL1-3 have single TDU motif, whereas VGLL4 has two tandem TDU motifs, suggesting that VGLL4 has distinct molecular functions among this family. Although molecular and physiological functions of VGLL members are still obscure, emerging evidence has shown that these members are involved in tumor development. Gene alterations and elevated expression of VGLL1-3 were observed in various types of tumors, and VGLL1-3 have been shown to possess tumorigenic functions. In contrast, down-regulation of VGLL4 was detected in various tumors, and the tumor-suppressing role of VGLL4 has been demonstrated. In this review, we summarize the recently identified multiple roles of VGLL members in tumor development and provide important and novel insights regarding tumorigenesis.