Elucidating the gene regulatory networks modulating cancer stem cells and non-stem cancer cells in high grade serous ovarian cancer

Genomics. 2019 Jan;111(1):103-113. doi: 10.1016/j.ygeno.2018.01.006. Epub 2018 Feb 6.

Abstract

The origin and pathogenesis of epithelial ovarian cancer have perplexed investigators for decades. The most prevalent type of it is the high-grade serous ovarian carcinoma (HGSOv) which is a highly aggressive disease with high relapse rates and insurgence of chemo-resistance at later stages of treatment. These are driven by a rare population of stem cell like cancer cells called cancer stem cells (CSCs). We have taken up a systems approach to find out the common gene interaction paths between non-CSC tumor cells (CCs) and CSCs in HGSOv. Detailed investigation reveals a set of 17 Transcription Factors (named as pivot-TFs) which can govern changes in the mode of gene regulation along these paths. Overall, this work highlights a divergent road map of functional information relayed by these common key players in the two cell states, which might aid towards designing novel therapeutic measures to target the CSCs for ovarian cancer therapy.

Keywords: Cancer stem cell; Gene expression; Ovarian cancer; Pivot genes; Pivot transcription factors; Serous ovarian cancer; Shortest path.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial / genetics*
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Neoplastic Stem Cells / physiology*
  • Ovarian Neoplasms / genetics*
  • Protein Interaction Domains and Motifs