SKA3-mediated hypoxia tolerance and metabolic reprogramming promote liver metastasis in lung adenocarcinoma.

ABSTRACT: Late-stage lung adenocarcinoma (LUAD) frequently results in distant metastasis, with liver metastasis indicating the poorest prognosis. To successfully colonize the liver, metastatic LUAD cells must overcome its relatively hypoxic microenvironment. This study explores the metabolic adaptations that facilitate LUAD liver metastasis, identifying Spindle and Kinetochore Associated Protein 3 (SKA3) as a critical mediator. Under hypoxic conditions, SKA3 expression is significantly upregulated, driving glucose metabolic reprogramming in LUAD cells to enable survival within the liver's hypoxic niche. Mechanistically, SKA3 competitively binds to prolyl hydroxylase domain-containing protein 2 (PHD2), disrupting its interaction with hypoxia-inducible factor 1-alpha (HIF-1α). Consequently, stabilized

SUBMITTER: Sun Z 

PROVIDER: S-EPMC12827483 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature