CBX3 confers ferroptosis resistance during blood-borne metastasis.

ABSTRACT: The survival mechanisms of circulating tumor cells (CTCs) remain poorly understood while these rare cell populations transit through the blood stream and colonize distant organs including the brain. Using single-cell RNA-seq of microfluidically-enriched CTCs and patient-matched brain metastatic tumor cells of lung adenocarcinoma (LUAD), we revealed CTC-selective upregulation of core gene signatures associated with ferroptosis. The malignancy of CTCs was confirmed through comparative genomic instability and copy number variation (CNV) analyses of paired CTCs and metastatic tumor cells using both transcriptomic and whole-exome sequencing. Among the transcription factors elevated in CTCs, Chromobox 3 (CBX3) was the top hit, which was tightly correlated with GPX4 expression. Functionally, CBX3

SUBMITTER: Wu C 

PROVIDER: S-EPMC12809899 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature