DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer

Yangchun Xie, Feimei Kuang, Jiao Liu, Daolin Tang, Rui Kang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Ferroptosis is a oxidative damage-dependent form of regulated cell death that has become an emerging target for disease prevention and treatment. Here, we show that dual-specificity phosphatase 1 (DUSP1), a phosphatase playing multiple roles in stress-signaling pathways, is a new repressor of ferroptosis in human pancreatic cancer cells. Several classical ferroptosis activators (eg, erastin and RSL3) induce the expression of DUSP1, but not other members of DUSP, which depends on extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Moreover, shRNA-mediated DUSP1 knockdown increases the anticancer activity of ferroptosis activators in pancreatic cancer cells through activating lipid peroxidation in vitro and in vivo. Importantly, DUSP1-mediated autophagy is responsible for lipid peroxidation-mediated ferroptotic cell death. Thus, the DUSP1-related ferroptotic pathway may represent a potential target for therapeutic intervention in pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalJournal of Pancreatology
Volume3
Issue number3
DOIs
StatePublished - Sep 1 2020

Keywords

  • Dual-specificity phosphatase 1
  • Ferroptosis
  • Pancreatic cancer

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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