Heterochromatin as a regulator of migratory cell populations in cervical cancers

The emergence of migratory populations of cells within solid cancers is an early, rate limiting step during cancer metastasis. We have previously reported the presence of one such population, a CD66+ve subset of cells in cervical cancer cell lines and primary tumours (Bajaj et al., 2011, Pattabiraman et al., 2014, Ammothumkandy et al., 2016). These populations show enhanced stemness, migration, invasion, and associations with metastasis. It is unclear what broad mechanisms regulate such migratory populations, and how these mechanisms would allow a “memory” of initial migration signalling cues during metastasis. It is also unknown how these mechanisms would allow cell fate plasticity, the switch between proliferative and migratory states, allowing the formation of proliferating distant metastases.

 We are now examining heterochromatin as a regulator of migratory populations in cervical cancers.  In contrast to mutations, heterochromatin based changes can retain a “memory” of signalling cues while still allowing plasticity, through metastable changes in chromatin conformation. We have focussed on the role of a heterochromatin regulator, the histone methyltransferase Suv39H1, in regulating migratory populations. We use a combination of cell culture based assays, molecular biology, genomics, data mining, and immunohistochemistry to understand the role of Suv39H1-regulated chromatin in controlling migratory populations.