CREB5 promotes nodal metastasis of cervical cancer by regulation of APLN-induced lymphangiogenesis.

ABSTRACT: Lymph node metastasis (LNM), a hallmark of aggressive cervical cancer (CCa), severely compromises prognosis and limits therapeutic efficacy. Despite its clinical significance, the molecular mechanisms driving LNM in CCa remain poorly characterized, necessitating urgent exploration. In this study, leveraging an in vitro lymphangiogenesis screening model, we identified CREB5 as a gene markedly upregulated in metastatic CCa, with its expression strongly correlating with LNM and poor patient survival. Mechanistic investigations revealed that CREB5 transcriptionally activates apelin (APLN) by directly binding to its canonical TGACG motif in the promoter region, thereby driving APLN-mediated lymphangiogenesis. Inhibition of CREB5 or treatment with ML221, a selective APLN receptor (APLNR) antagon

SUBMITTER: Xia M 

PROVIDER: S-EPMC12559322 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature