VGLL4
Overview
VGLL4 (Vestigial Like Family Member 4) is a negative regulator of the Hippo signaling pathway, competing with YAP1/TAZ for TEAD transcription factor binding. Deletion of VGLL4 in esophageal squamous cell carcinoma (ESCC) removes this negative regulator and is associated with the ESCC1 molecular subtype alongside YAP1 amplification.
Alterations observed in the corpus
- Novel 3p25.2 focal deletion in ESCC removing VGLL4, a Hippo-pathway negative regulator; the deletion also encompasses adjacent ATG7; associated with the ESCC1 molecular subtype in the TCGA integrated esophageal/GEA analysis PMID:28052061
Cancer types (linked)
- ESCC: 3p25.2 deletion of VGLL4 identified in the ESCC1 subtype (NRF2-pathway / classical squamous); co-occurs with YAP1 amplification at 11q22.1, suggesting combined Hippo pathway dysregulation PMID:28052061
Co-occurrence and mutual exclusivity
- Deletion co-occurs with YAP1 amplification in ESCC1, pointing to coordinated Hippo pathway activation through loss of a negative regulator plus gain of a positive effector PMID:28052061
- Adjacent ATG7 (autophagy component) is also deleted at 3p25.2, co-occurring with NFE2L2 pathway alterations in ESCC1 PMID:28052061
Therapeutic relevance
- ESCC1 with VGLL4 deletion and YAP1 amplification may be amenable to Hippo/YAP1-targeted therapeutic approaches, though no clinical trials are reported in the corpus PMID:28052061
Open questions
- The functional consequence of VGLL4 loss in ESCC1 versus YAP1 amplification as independent vs. co-operative Hippo dysregulation mechanisms has not been experimentally resolved.
Sources
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