Hyperoxia induces metabolic starvation and suppresses lung cancer progression through the CKMT1-AMPK axis

ABSTRACT: Tumor hypoxia promotes malignant progression and therapeutic resistance, yet the molecular consequences of hyperoxia in cancer remain poorly defined. Here we report an unexpected clinical observation in which a patient with lung cancer exhibited marked tumor regression during hyperbaric oxygen therapy for peripheral arterial disease. This observation prompted us to investigate the molecular effects of hyperoxia in lung cancer models. We found that hyperoxic exposure disrupts the mitochondrial creatine kinase (CKMT1)–mediated energy-transfer system, leading to an imbalance in the adenine nucleotide pool and metabolic energy stress in cancer cells. This energetic crisis activates the tumor suppressor AMP-activated protein kinase (AMPK) and suppresses cancer cell proliferation. Together, our findings identify CKMT1 dysfunction and AMPK activation as central mediators of hyperoxia-induced tumor suppression and suggest that targeting tumor energy-transfer systems may represent a therapeutic strategy for lung cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE352516 | GEO | 2026/11/02

REPOSITORIES: GEO