Fig. 7
Working model of KRAS/KRASG12D-triggered HCC in response to high FBXL6 expression. FBXL6 elevation facilitates the KRAS/KRASG12D mutation-mediated activation of MEK/ERK/mTOR signaling by promoting K63-linked KRAS/KRASG12D polyubiquitination at the site K128. Hyperactive mTOR increases the expression of PRELID2, leading to HCC tumorigenesis and metastasis in mice. This picture was created by BioRender. FBXL6 F-box and leucine-rich repeat 6, KRAS kirsten rat sarcoma, PRELID2 the proteins of relevant evolutionary and lymphoid interest (PRELI) domain 2, HCC hepatocellular carcinoma, MEK mitogen-activated protein kinase kinase, ERK extracellular signal-regulated kinase, mTOR mammalian target of rapamycin, WT wild-type, Ub ubiquitin, ROS reactive oxygen species