Fig. 6

Sulfarotene targets the SOS2-RAS signal nexus. a Dynamic expression changes in SOS2 and associated neighboring genes in response to sulfarotene treatment. Expression changes of SOS2 and its 220 related genes in Hep3B-TRCs after treatment with sulfarotene at 1 and 5 µM for 2 days were revealed by RNA-Seq analysis (|PCCs| > 0.9, P < 0.05) and presented as a network diagram. b Heat map presentation of SOS2-associated KEGG pathways in response to sulfarotene treatment abstracted from 4 differential, dynamic change patterns of clusters 2, 3, 4 and 7. c Upregulation of phosphorylation of several types of RTKs in HCC TRCs as detected by human phospho-RTK arrays compared to that in parental HCC cancer cells. Left, representative real-time intensity images of the phospho-RTK arrays. Right, summary of the upregulated phospho-RTKs in bar graphs. d-e Dose-dependent inhibition of GTP-RAS, SOS2 and associated PI3K/AKT and MEK/ERK pathway mediators by sulfarotene in association with the promotion of RARα in the HCC TRCs. Hep3B-TRCs and PLC/PRF5-TRCs were treat with sulfarotene at concentrations of 1.0 to 5.0 µM for 48 h, and cell lysates were subjected to western blot analyses for the respective proteins as indicated