
@article {66851,
	title = {Notch signalling in cervical cancer.},
	journal = {Exp Cell Res},
	year = {2019},
	month = {2019 Oct 18},
	pages = {111682},
	abstract = {<p>The initial discovery of key developmental signalling pathways, largely using classical genetic approaches in model organisms, was followed by an intense burst of characterisation of the molecular components. Studies also began demonstrating a role for these pathways in oncogenesis. Patterns of mutations in Notch pathway components, such as those reported in sub-sets of hematological malignancies, have been easier to study, and the cumulative information is leading to potentially new therapies. However, it has been more challenging to clearly define the role of the Notch pathway in human solid tumours, given the absence of widespread specific activating or repressive mutations in key components of the pathway. In this review, we trace more than two decades of work looking at the role of Notch signalling in human cervical cancer progression. We document the contrasting reports on a tumour suppressive role and pro-oncogenic role in cervical cancers. However, an analysis of recent genomic data strikingly shows both widespread features of Notch expression and genetic changes that largely amplify positive regulators and delete negative controllers of the Notch pathway. This analysis reinforces a largely pro-oncogenic role for Notch signalling and lays the foundation for a nuanced exploration of synergistic and targeted therapies. Lastly, we further trace some of the complex challenges in advanced cervical cancer progression, including issues of cancer stem cells and metastasis.</p>
},
	issn = {1090-2422},
	doi = {10.1016/j.yexcr.2019.111682},
	author = {Rodrigues, Calvin and Joy, Leanna R and Sachithanandan, Sasikala P and Krishna, Sudhir}
}
@article {53190,
	title = {A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells.},
	journal = {Exp Cell Res},
	year = {2019},
	month = {2019 Feb 14},
	abstract = {<p>Metastatic progression is a major cause of mortality in cervical cancers, but factors regulating migratory and pre-metastatic cell populations remain poorly understood. Here, we sought to assess whether a SUV39H1-low chromatin state promotes migratory cell populations in cervical cancers, using meta-analysis of data from The Cancer Genome Atlas (TCGA), immunohistochemistry, genomics and functional assays. Cervical cancer cells sorted based on migratory ability in vitro have low levels of SUV39H1 protein, and SUV39H1 knockdown in vitro enhanced cervical cancer cell migration. Further, TCGA SUV39H1-low tumours correlated with poor clinical outcomes and showed gene expression signatures of cell migration. SUV39H1 expression was examined within biopsies, and SUV39H1 cells within tumours also demonstrated migratory features. Next, to understand genome scale transcriptional and chromatin changes in migratory populations, cell populations sorted based on migration in vitro were examined using RNA-Seq, along with ChIP-Seq for H3K9me3, the histone mark associated with SUV39H1. Migrated populations showed SUV39H1-linked migratory gene expression signatures, along with broad depletion of H3K9me3 across gene promoters. We show for the first time that a SUV39H1-low chromatin state associates with, and promotes, migratory populations in cervical cancers. Our results posit SUV39H1-low cells as key populations for prognosis estimation and as targets for novel therapies.</p>
},
	issn = {1090-2422},
	doi = {10.1016/j.yexcr.2019.02.010},
	author = {Rodrigues, Calvin and Pattabiraman, Chitra and Vijaykumar, Anjali and Arora, Reety and Narayana, Suma Mysore and Kumar, Rekha V and Notani, Dimple and Varga-Weisz, Patrick and Krishna, Sudhir}
}
