USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation

Pingping Hou, Xingdi Ma, Qiang Zhang, Chang Jiun Wu, Wenting Liao, Jun Li, Huamin Wang, Jun Zhao, Xin Zhou, Carolyn Guan, Jeffery Ackroyd, Shan Jiang, Jianhua Zhang, Denise J. Spring, Y. Alan Wang, Ronald A. DePinho

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential drug-gable target for this intractable disease.

Original languageEnglish (US)
Pages (from-to)1361-1366
Number of pages6
JournalGenes and Development
Volume33
Issue number19-20
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine

Keywords

  • Cancer stemness
  • Deubiquitinase
  • Pancreatic cancer
  • TCF7
  • USP21
  • Wnt pathway

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