Reprogramming lineage features promotes epithelial behavior in carcinoma cells [ATAC-seq]

At the same time, expression of identity-discordant lineage determinants can significantly shift cell phenotype by creating lineage hybrid states. One example is the misexpression of IKZF3, encoding the lymphocyte restricted transcription factor Aiolos, by roughly half of non-small cell lung carcinomas (NSCLC) and the majority of small cell lung carcinomas [1].

During normal lymphocyte development, pre-B progenitors enter a proliferative phase dependent on survival cues from bone marrow stroma. To progress, Aiolos and its paralog Ikaros (IKZF1) repress multiple adhesion-related genes, releasing cells from this epithelial-type dependence on solid matrix in preparation for their release as mature lymphocytes into the circulation [2, 3]. In lung cancers, unlicensed expression of Aiolos initiates a similar shift from an epithelial to a lymphocyte-like state by repression of multiple adhesion-related genes, resulting in loss of anoikis and consequent metastatic spread [1].