Complex HuR function in pancreatic cancer cells

Jonathan R. Brody, Dan A. Dixon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal patient outcomes. The underlying core genetic drivers of disease have been identified in human tumor specimens and described in genetically engineered mouse models. These genetic drivers of PDAC include KRAS signaling, TP53 mutations, and genetic loss of the SMAD4 tumor suppressor protein. Beyond the known mutational landscape of PDAC genomes, alternative disrupted targets that extend beyond conventional genetic mutations have been elusive and understudied in the context of PDAC cell therapeutic resistance and survival. This last point is important because PDAC tumors have a unique and complex tumor microenvironment that includes hypoxic and nutrient-deprived niches that could select for cell populations that garner therapeutic resistance, explaining tumor heterogeneity in regards to response to different therapies. We and others have embarked in a line of investigation focused on the key molecular mechanism of posttranscriptional gene regulation that is altered in PDAC cells and supports this pro-survival phenotype intrinsic to PDAC cells. Specifically, the key regulator of this mechanism is a RNA-binding protein, HuR (ELAVL1), first described in cancer nearly two decades ago. Herein, we will provide a brief overview of the work demonstrating the importance of this RNA-binding protein in PDAC biology and then provide insight into ongoing work developing therapeutic strategies aimed at targeting this molecule in PDAC cells. This article is categorized under: RNA in Disease and Development > RNA in Disease.

Original languageEnglish (US)
Article numbere1469
JournalWiley interdisciplinary reviews. RNA
Volume9
Issue number3
DOIs
StatePublished - May 1 2018
Externally publishedYes

Keywords

  • ELAVL1
  • HuR
  • RNA binding proteins
  • pancreatic cancer
  • pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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