Inhibition of JNK in K562/A02 cells by JIP (Figure 4D), a peptide inhibitor specifically targeting JNK [36,37], or by transfection K562/A02 and KB/VCR cells (Figure 4E) with JNK1(APF), a plasmid of dominant negative mutant of JNK [38], abundantly impaired the Gli activity in chemoresistant cancer cells as judged by Gli-luciferase reporter assay, therefore suggesting that JNK is required for maintaining the cell-autonomous Gli activation in acquired chemoresistant cancer cells. Here, SMAD4 is linked to cancer.