{Reference Type}: Journal Article
{Title}: YAP inhibits NF-κB signaling and ccRCC growth by opposing p65-ZHX2 cooperativity.
{Author}: Li X;Cho YS;Liu Y;Yang Y;Zhuo S;Jiang J;
{Journal}: bioRxiv
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 27
暂无{DOI}: 10.1101/2024.06.21.600079
{Abstract}: Hippo pathway functions as a tumor suppressor pathway by inhibiting the oncogenic potential of pathway effectors YAP/TAZ. However, YAP can also function as a context-dependent tumor suppressor in several types of cancer including clear cell renal cell carcinomas (ccRCC). Here we show that YAP blocks NF-κB signaling in ccRCC to inhibit cancer cell growth. Mechanistically, YAP inhibits the expression of ZHX2, a critical p65 co-factor in ccRCC. Furthermore, YAP competes with ZHX2 for binding to p65. Consequently, elevated nuclear YAP blocks the cooperativity between ZHX2 and p65, leading to diminished NF-κB target gene expression. Pharmacological inhibition of Hippo/MST1/2 blocked NF-κB transcriptional program and suppressed ccRCC cancer cell growth, which can be rescued by ZHX2/p65 overexpression. Our study uncovers a novel crosstalk between the Hippo and NF-κB pathways and its involvement in ccRCC growth inhibition, suggesting that targeting the Hippo pathway may provide a therapeutical opportunity for ccRCC treatment.