A Nature Communications study identified a discrete subset of tumor cells—tight junction‑high and CDH17‑positive—that act as primary instigators of colorectal cancer liver metastases. The authors mapped transcriptional and phenotypic features that distinguish these cells and traced their colonization programs in preclinical models. The paper delineates molecular signatures and surface markers suitable for targeted interception of the metastatic cascade and suggests that blocking the seeding capacity of these cells could prevent liver colonization. The findings provide a cellularly focused roadmap for anti-metastatic strategies and biomarker development in colorectal cancer.