Schlafen 5 as a novel therapeutic target in pancreatic ductal adenocarcinoma

Mariafausta Fischietti, Frank Eckerdt, Gavin T. Blyth, Ahmet D. Arslan, William M. Mati, Chidera V. Oku, Ricardo E. Perez, Catalina Lee-Chang, Ewa M. Kosciuczuk, Diana Saleiro, Elspeth M. Beauchamp, Maciej S. Lesniak, Daniela Verzella, Leyu Sun, Eleanor N. Fish, Guang Yu Yang, Wenan Qiang, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We provide evidence that a member of the human Schlafen (SLFN) family of proteins, SLFN5, is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Targeted deletion of SLFN5 results in decreased PDAC cell proliferation and suppresses PDAC tumorigenesis in in vivo PDAC models. Importantly, high expression levels of SLFN5 correlate with worse outcomes in PDAC patients, implicating SLFN5 in the pathophysiology of PDAC that leads to poor outcomes. Our studies establish novel regulatory effects of SLFN5 on cell cycle progression through binding/blocking of the transcriptional repressor E2F7, promoting transcription of key genes that stimulate S phase progression. Together, our studies suggest an essential role for SLFN5 in PDAC and support the potential for developing new therapeutic approaches for the treatment of pancreatic cancer through SLFN5 targeting.

Original languageEnglish (US)
Pages (from-to)3273-3286
Number of pages14
JournalOncogene
Volume40
Issue number18
DOIs
StatePublished - May 6 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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