VGLL4 inhibits YAP1/TEAD signaling to suppress the epidermal squamous cell carcinoma cancer phenotype

Autor: McKayla B. Mickle, Gautam Adhikary, Wen Xu, Richard L. Eckert, Suruchi Shrestha
Rok vydání: 2021
Předmět:
Zdroj: Mol Carcinog
ISSN: 1098-2744
0899-1987
Popis: Epidermal squamous cell carcinoma develops in response to ultraviolet light exposure and is among the most common cancers. The transglutaminase 2 cancer cell survival protein stimulates activity of the YAP1/TEAD transcription complex to drive expression of genes that promote aggressive epidermal squamous cell carcinoma cell invasion, migration and tumor formation. Therefore, we are interested in mechanisms that may inhibit these events. Vestigial-like protien-4 (VGLL4) is a transcription cofactor/tumor suppressor that inhibits several pro-cancer pathways including YAP1 signaling. Our present studies show that VGLL4 inhibits YAP1/TEAD-dependent transcription to reduce expression of YAP1 target genes (CCND1, CYR61 and CTGF) and pro-cancer collagen genes (COL1A2, COL3A1). We further show that loss of these YAP1 regulated genes is required for VGLL4 suppression of the cancer cell phenotype, as forced CCND1 or COL1A2 expression partially restores the aggressive cancer phenotype in VGLL4 expressing cells. Consistent with these findings, VGLL4 expression reduces tumor formation, and this is associated with reduced CCND1, CYR61, CTGF, COL1A2 and COL1A3 mRNA and protein level, and reduced EMT marker expression. These findings indicate that VGLL4 suppresses the malignant epidermal squamous cell carcinoma cancer phenotype by inhibiting YAP1/TEAD-dependent pro-cancer signaling.
Databáze: OpenAIRE
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