A Suv39H1-low chromatin state drives migratory cell populations in cervical cancer [ChIP-Seq]

ABSTRACT: The evolution of migratory populations of cells within solid tumours represents a critical stage during cancer metastasis. We have previously reported the enhanced migratory properties of one such population, marked by the expression of CD66, within cervical cancers. However, it is not clear what mechanisms drive such migratory populations, and how these cells would retain a “memory” of initial migration-inducing cues during metastasis. Here, we describe the role of a Suv39H1-low heterochromatin state as a driver of cervical cancer migratory populations. Cervical cancer cells were sorted based on migratory ability in vitro. These migrated populations show low Suv39H1, and Suv39H1 knockdown enhances cell migration. Using histopathology to examine clinical carcinoma progression, initial progression showed expansion of a proliferative Suv39H1high population, followed by the emergence of a sarcomatoid, migratory Suv39H1low cell population in advanced stages. Additionally, meta-analysis of TCGA data revealed that low tumoural Suv39H1 also correlated with lower patient survival, and with expression signatures of migration, TGF-β signalling, and links with a CD66 cell signature. Lastly, using RNA-Seq and H3K9me3 ChIP-Seq on migrated populations in vitro, it was observed that these populations show Suv39H1-linked transcriptome alterations and broad scale H3K9me3 remodelling. This Suv39H1-linked heterochromatin regulation could explain plasticity in migratory and metastatic populations, and allows for a “memory” of migration inducing cues, through metastable changes in chromatin conformation. The understanding of such regulatory mechanisms in migratory populations may prove valuable in efforts to develop anti-metastatic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103793 | GEO | 2019/03/01

REPOSITORIES: GEO