Proteome Instability Is a Therapeutic Vulnerability in Mismatch Repair-Deficient Cancer

Daniel J. McGrail, Jeannine Garnett, Jun Yin, Hui Dai, David J.H. Shih, Truong Nguyen Anh Lam, Yang Li, Chaoyang Sun, Yongsheng Li, Rosemarie Schmandt, Ji Yuan Wu, Limei Hu, Yulong Liang, Guang Peng, Eric Jonasch, David Menter, Melinda S. Yates, Scott Kopetz, Karen H. Lu, Russell BroaddusGordon B. Mills, Nidhi Sahni, Shiaw Yih Lin

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


McGrail et al. find that the abundance of destabilizing mutations in microsatellite unstable (MSI) tumors causes proteome instability and accumulation of misfolded proteins. To compensate, MSI tumors rely on a Nedd8-mediated pathway to clear misfolded aggregates, which can be therapeutically targeted by MLN4924.

Original languageEnglish (US)
Pages (from-to)371-386.e12
JournalCancer Cell
Issue number3
StatePublished - Mar 16 2020


  • colorectal cancer (COAD)
  • endometrial cancer (UCEC)
  • immunotherapy
  • microsatellite instability (MSI)
  • mismatch repair (MMR)
  • neddylation
  • protein degredation
  • protein homeostasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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