Inhibition of primary cilia-hedgehog signaling axis triggers autophagic cell death and suppresses malignant progression of VHL wild-type ccRCC.

ABSTRACT: Primary cilia are present on renal tubules and are implicated to play a pivotal role in transducing signals during development; however, the oncogenic role of cilia in clear cell renal cell carcinoma (ccRCC) has not been examined. Here we show that VHL wild-type ccRCC cell lines have a high incidence of primary cilia, and a high frequency of primary cilia is positively correlated with VHL expression and poor prognosis. Besides, the depletion of KIF3A and IFT88, genes required for ciliogenesis, significantly inhibited tumor proliferation and metastasis in vitro and in vivo. Further analysis found that mutations of key genes in hedgehog signaling are enriched in VHL wild ccRCC, its downstream signaling activation depends on ciliogenesis. Moreover, depletion of primary cilia or suppression of

SUBMITTER: Tian S 

PROVIDER: S-EPMC11466958 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature