Vestigial-like 1 (VGLL1): An ancient co-transcriptional activator linking wing, placenta, and tumor development

Vestigial-like 1 (VGLL1) is a recently discovered driver of proliferation and invasion that is expressed in many aggressive human malignancies and is strongly associated with poor prognosis. The VGLL1 gene encodes for a co-transcriptional activator that shows intriguing structural similarity to key activators in the hippo pathway, providing important clues to its functional role. VGLL1 binds to TEAD transcription factors in an analogous fashion to YAP1 but appears to activate a distinct set of downstream gene targets. In mammals, VGLL1 expression is found almost exclusively in placental trophoblasts, cells that share many hallmarks of cancer. Due to its role as a driver of tumor progression, VGLL1 has become a target of interest for potential anticancer therapies. In this review, we discuss VGLL1 from an evolutionary perspective, contrast its role in placental and tumor development, summarize the current knowledge of how signaling pathways can modulate VGLL1 function, and discuss potential approaches for targeting VGLL1 therapeutically.