Article
Dynamic transitioning between MAPK-driven and WNT-driven cell states drives intestinal cancer and shapes therapy response.
Nature genetics - 1 Jun 2026
Moore Amanda R, Biehs Brian, Kljavin Noelyn, Nguyen Thi Thu Thao, Shah Akansha, Burton Jeremy, Jiang Honglin, Tan Jenille, Chakroborty Deepankar, Wang Lisa, Chaudhary Nayan, He Dongze, Lin William, Mesh Kathryn, Ye Xin, Bhat Kamakoti P, Tai Lisa, Xie Shiqi, Ye Weilan, McGinnis Lisa, Malek Shiva, Melo Sandra P, de Sauvage Frederic J
Abstract excerpt
Colorectal cancer (CRC) frequently harbors activating mutations in the WNT and MAPK pathways. While KRAS mutations alone can drive tumor initiation in many tissues, they are insufficient in the intestine. Leveraging allele-specific properties of RAS, we developed a mouse model to investigate MAPK hyperactivation. Here we show that KRAS mutations drive a regenerative state while antagonizing the Lgr5+ intestinal...
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