The Hippo pathway effector YAP inhibits NF-κB signaling and ccRCC growth by opposing ZHX2.

ABSTRACT: The prevailing view in the cancer field is that Hippo signaling pathway functions as a tumor suppressor pathway by blocking the oncogenic potential of the pathway effectors Yes1 associated transcriptional regulator (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ). However, YAP can also function as a context-dependent tumor suppressor in several types of cancer including clear cell renal cell carcinomas (ccRCC). We find that, in additional to inhibiting hypoxia-inducible factor 2α (HIF2α), a major oncogenic driver in Von Hippel-Lindau (VHL)-/- ccRCC, YAP also blocks nuclear factor κB (NF-κB ) signaling in ccRCC to inhibit cancer cell growth under conditions where HIF2α is dispensable. Mechanistically, YAP inhibits the expression of Zinc fingers and homeoboxes 2 (

SUBMITTER: Li X 

PROVIDER: S-EPMC11230290 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature