Article
Proteome Instability Is a Therapeutic Vulnerability in Mismatch Repair-Deficient Cancer.
Cancer cell - 16 Mar 2020
McGrail Daniel J, Garnett Jeannine, Yin Jun, Dai Hui, Shih David J H, Lam Truong Nguyen Anh, Li Yang, Sun Chaoyang, Li Yongsheng, Schmandt Rosemarie, Wu Ji Yuan, Hu Limei, Liang Yulong, Peng Guang, Jonasch Eric, Menter David, Yates Melinda S, Kopetz Scott, Lu Karen H, Broaddus Russell, Mills Gordon B, Sahni Nidhi, Lin Shiaw-Yih
Abstract excerpt
Deficient DNA mismatch repair (dMMR) induces a hypermutator phenotype that can lead to tumorigenesis; however, the functional impact of the high mutation burden resulting from this phenotype remains poorly explored. Here, we demonstrate that dMMR-induced destabilizing mutations lead to proteome instability in dMMR tumors, resulting in an abundance of misfolded protein aggregates. To compensate, dMMR cells utilize...
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