Article
SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers.
Nature communications - 12 Sept 2024
Lilja Johanna, Kaivola Jasmin, Conway James R W, Vuorio Joni, Parkkola Hanna, Roivas Pekka, Dibus Michal, Chastney Megan R, Varila Taru, Jacquemet Guillaume, Peuhu Emilia, Wang Emily, Pentikäinen Ulla, Martinez D Posada Itziar, Hamidi Hellyeh, Najumudeen Arafath K, Sansom Owen J, Barsukov Igor L, Abankwa Daniel, Vattulainen Ilpo, Salmi Marko, Ivaska Johanna
Abstract excerpt
The KRAS oncogene drives many common and highly fatal malignancies. These include pancreatic, lung, and colorectal cancer, where various activating KRAS mutations have made the development of KRAS inhibitors difficult. Here we identify the scaffold protein SH3 and multiple ankyrin repeat domain 3 (SHANK3) as a RAS interactor that binds active KRAS, including mutant forms, competes with RAF and limits oncogenic...
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