HECTD4 and neoplasm: Here, we conducted a genome-wide in vivo CRISPR-inactivation (CRISPR-i) screen using cultured breast CTCs, identifying HECTD4, a previously uncharacterized member of the Homologous to E6AP C-Terminus (HECT) ubiquitin ligase gene family, as a suppressor of tumor initiation in a model of lung metastasis.