NSMF modulates replication stress to facilitate colorectal cancer progression.

ABSTRACT: Cancer cells precisely modulate replication stress to sustain genomic instability without triggering lethal DNA damage, yet regulators enabling this delicate balance remain largely unknown. Here, we identify N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF) as a novel and critical regulator of replication stress in colorectal cancer (CRC). NSMF expression is significantly elevated in CRC tissues and correlates closely with elevated replication stress. In ApcMin/+ mouse models, Nsmf knockout selectively induces replication-dependent DNA damage in tumor tissues, suppressing tumor growth and prolonging survival, without harming normal tissues. Mechanistically, NSMF deficiency impairs replication fork progression under stress conditions, resulting in D

SUBMITTER: Shin KJ 

PROVIDER: S-EPMC12802900 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature