Hypoxia-induced metastatic heterogeneity in pancreatic cancer.

ABSTRACT: In most solid tumors, hypoxia constitutes a defining microenvironmental feature that reprograms malignant cells into a highly metastatic state by driving cellular plasticity and exacerbating chromosomal instability (CIN). However, the mechanisms by which cancer cells concurrently co-opt these elements of hypoxic adaptation to promote metastasis remains poorly understood. Here, we report that hypoxia promotes metastasis by suppressing the JmjC-containing histone lysine demethylase Kdm8. CRISPR/Cas9-mediated targeting of Kdm8 in a Kras;Trp53-driven mouse model of pancreatic ductal adenocarcinoma (PDA) robustly rewires the malignant cell transcriptomic programs, leading to a profound loss of the epithelial morphology and widespread metastatic disease. In PDA patients, a h

SUBMITTER: Gunasekaran PM 

PROVIDER: S-EPMC12407890 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature