A Suv39H1-low chromatin state drives migratory cell populations in cervical cancers

Abstract

AbstractThe emergence of migratory cell populations within tumours represents a critical early stage during cancer metastasis. We have previously reported one such population, marked by CD66, in cervical cancers. It is unclear what broad mechanisms regulate such migratory populations. Here, we describe the role of a Suv39H1-low heterochromatin state as a driver of cervical cancer migratory populations. Cervical cancer cells sorted based on migratory ability in vitro show low Suv39H1, and Suv39H1 knockdown enhances cell migration. Histopathology shows the emergence of migratory Suv39H1low populations in advanced carcinoma progression. Meta-analysis of data from The Cancer Genome Atlas (TCGA) reveals that Suv39H1-low tumours show migration and CD66 expression signatures, and correlate with lower patient survival. Lastly, genome-wide profiling of migrated populations using RNA-Seq and H3K9me3 ChIP-Seq reveals Suv39H1-linked transcriptome alterations and a broad loss of H3K9me3, suggesting an increase in chromatin plasticity in migrated populations. The understanding of such chromatin based regulation in migratory populations may prove valuable in efforts to develop anti-metastatic strategies.