News Finding: The researchers thus provide a possible explanation for why these drugs are not effective in colorectal cancer.
Paper Finding: In HCT116, the stabilizing effect of XAV939 on AXIN1 overrode the reduction of AXIN1 levels caused by trametinib ( Supplementary Fig.
News Context: The researchers thus provide a possible explanation for why these drugs are not effective in colorectal cancer. Depending on the Wnt activity, the cancer cells can switch back and forth between the stem cell state and a differentiated state. At the same time, the gene activity of the cancer cells changed to a stem cell-typical pattern.
Paper Context: Inhibition of tankyrases by XAV939 prevents degradation of AXIN1, leading to reduced Wnt activity . In HCT116, the stabilizing effect of XAV939 on AXIN1 overrode the reduction of AXIN1 levels caused by trametinib ( Supplementary Fig. As a result, trametinib was unable to induce AXIN2 expression in the presence of XAV939.