HNF1A is a Novel Oncogene That Regulates Human Pancreatic Cancer Stem Cell Properties

Overview

Journal Elife

Specialty Biology

Date 2018 Aug 4

PMID 30074477

Citations 36

Authors

Ethan V Abel

Masashi Goto

Brian Magnuson

Saji Abraham

Nikita Ramanathan

Emily Hotaling

Anthony A Alaniz

Chandan Kumar-Sinha

Michele L Dziubinski

Sumithra Urs

Lidong Wang

Jiaqi Shi

Meghna Waghray

Mats Ljungman

Howard C Crawford

Diane M Simeone

Affiliations

Soon will be listed here.

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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