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The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors
Cancer cells bearing distinct KRAS mutations exhibit variable sensitivity to SHP2 inhibitors (SHP2i). Here we show that cells harboring KRAS Q61H are uniquely resistant to SHP2i, and investigate the underlying mechanisms using biophysics, molecular dynamics, and cell-based approaches. Q61H mutation...
Autores principales: | Gebregiworgis, Teklab, Kano, Yoshihito, St-Germain, Jonathan, Radulovich, Nikolina, Udaskin, Molly L., Mentes, Ahmet, Huang, Richard, Poon, Betty P. K., He, Wenguang, Valencia-Sama, Ivette, Robinson, Claire M., Huestis, Melissa, Miao, Jinmin, Yeh, Jen Jen, Zhang, Zhong-Yin, Irwin, Meredith S., Lee, Jeffrey E., Tsao, Ming-Sound, Raught, Brian, Marshall, Christopher B., Ohh, Michael, Ikura, Mitsuhiko |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560773/ https://www.ncbi.nlm.nih.gov/pubmed/34725361 http://dx.doi.org/10.1038/s41467-021-26526-y |
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