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HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties. | LitMetric

AI Article Synopsis

  • The study investigates the role of pancreatic cancer stem cells (PCSCs) and identifies the transcription factor HNF1A as a key regulator of PCSC function.
  • Researchers found that higher levels of HNF1A in PCSCs led to increased growth and tumor formation, while its depletion caused reduced growth and cell death.
  • An HNF1A-dependent gene signature was linked to poorer survival outcomes in patients with pancreatic ductal adenocarcinoma (PDA), highlighting HNF1A's significance as an oncogene in this type of cancer.

Article Abstract

The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a human PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, decreased PCSC marker expression, and downregulation of expression. Conversely, HNF1A overexpression increased PCSC marker expression and tumorsphere formation in pancreatic cancer cells and drove pancreatic ductal adenocarcinoma (PDA) cell growth. Importantly, depletion of HNF1A in xenografts impaired tumor growth and depleted PCSC marker-positive cells in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of PCSC properties and novel oncogene in PDA.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122955PMC
http://dx.doi.org/10.7554/eLife.33947DOI Listing

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