The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors
SHP2 promotes RAS-driven MAPK signalling, but it is unclear why cancer cells with distinct KRAS mutations exhibit differential sensitivity to SHP2 inhibition. Here the authors show that KRAS Q61H is decoupled from SHP2- mediated upstream regulation, thus Q61H pancreatic cancer cells maintain MAPK si...
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Nature Portfolio
2021
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oai:doaj.org-article:adc5eaa39af340409424aef1fcf1144b2021-11-08T11:06:01ZThe Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors10.1038/s41467-021-26526-y2041-1723https://doaj.org/article/adc5eaa39af340409424aef1fcf1144b2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-26526-yhttps://doaj.org/toc/2041-1723SHP2 promotes RAS-driven MAPK signalling, but it is unclear why cancer cells with distinct KRAS mutations exhibit differential sensitivity to SHP2 inhibition. Here the authors show that KRAS Q61H is decoupled from SHP2- mediated upstream regulation, thus Q61H pancreatic cancer cells maintain MAPK signalling and are refractory to SHP2 inhibitors.Teklab GebregiworgisYoshihito KanoJonathan St-GermainNikolina RadulovichMolly L. UdaskinAhmet MentesRichard HuangBetty P. K. PoonWenguang HeIvette Valencia-SamaClaire M. RobinsonMelissa HuestisJinmin MiaoJen Jen YehZhong-Yin ZhangMeredith S. IrwinJeffrey E. LeeMing-Sound TsaoBrian RaughtChristopher B. MarshallMichael OhhMitsuhiko IkuraNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
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Science Q Teklab Gebregiworgis Yoshihito Kano Jonathan St-Germain Nikolina Radulovich Molly L. Udaskin Ahmet Mentes Richard Huang Betty P. K. Poon Wenguang He Ivette Valencia-Sama Claire M. Robinson Melissa Huestis Jinmin Miao Jen Jen Yeh Zhong-Yin Zhang Meredith S. Irwin Jeffrey E. Lee Ming-Sound Tsao Brian Raught Christopher B. Marshall Michael Ohh Mitsuhiko Ikura The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors |
| description |
SHP2 promotes RAS-driven MAPK signalling, but it is unclear why cancer cells with distinct KRAS mutations exhibit differential sensitivity to SHP2 inhibition. Here the authors show that KRAS Q61H is decoupled from SHP2- mediated upstream regulation, thus Q61H pancreatic cancer cells maintain MAPK signalling and are refractory to SHP2 inhibitors. |
| format |
article |
| author |
Teklab Gebregiworgis Yoshihito Kano Jonathan St-Germain Nikolina Radulovich Molly L. Udaskin Ahmet Mentes Richard Huang Betty P. K. Poon Wenguang He Ivette Valencia-Sama Claire M. Robinson Melissa Huestis Jinmin Miao Jen Jen Yeh Zhong-Yin Zhang Meredith S. Irwin Jeffrey E. Lee Ming-Sound Tsao Brian Raught Christopher B. Marshall Michael Ohh Mitsuhiko Ikura |
| author_facet |
Teklab Gebregiworgis Yoshihito Kano Jonathan St-Germain Nikolina Radulovich Molly L. Udaskin Ahmet Mentes Richard Huang Betty P. K. Poon Wenguang He Ivette Valencia-Sama Claire M. Robinson Melissa Huestis Jinmin Miao Jen Jen Yeh Zhong-Yin Zhang Meredith S. Irwin Jeffrey E. Lee Ming-Sound Tsao Brian Raught Christopher B. Marshall Michael Ohh Mitsuhiko Ikura |
| author_sort |
Teklab Gebregiworgis |
| title |
The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors |
| title_short |
The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors |
| title_full |
The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors |
| title_fullStr |
The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors |
| title_full_unstemmed |
The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors |
| title_sort |
q61h mutation decouples kras from upstream regulation and renders cancer cells resistant to shp2 inhibitors |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/adc5eaa39af340409424aef1fcf1144b |
| work_keys_str_mv |
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