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

    21 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
    • Cell Biology
    • Cancer Research


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