Elevated FBXL6 activates both wild-type KRAS and mutant KRASG12D and drives HCC tumorigenesis via the ERK/mTOR/PRELID2/ROS axis in mice

Abstract

FBXL6 activates KRAS or KRAS^G12D via ubiquitination at the site K128, leading to activation of the ERK/mTOR/PRELID2/ROS axis and tumorigenesis. Dual inhibition of MEK and mTOR effectively protects against FBXL6- and KRAS^G12D-induced tumorigenesis, providing a potential therapeutic strategy to treat this aggressive subtype of liver cancer.