News Finding: At the same time, the gene activity of the cancer cells changed to a stem cell-typical pattern.
Paper Finding: This finding indicates that GSK3B and MEK/ERK act on Wnt signalling by distinct mechanisms, which can be independently targeted by small molecules.
News Context: 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. "This corresponds exactly to the picture of the "sleeping cancer stem cells" that have been described in many types of cancer for several years," explains Tianzuo Zhan, clinician scientist at both the DKFZ and the Mannheim University Medical Center "These cells survive the therapy and are subsequently responsible for the relapse.
Paper Context: Surprisingly, we also observed that APC truncations synergize with MEK and ERK inhibition to activate Wnt, while they completely abolish the stimulating effect of GSK3B inhibitors. This finding indicates that GSK3B and MEK/ERK act on Wnt signalling by distinct mechanisms, which can be independently targeted by small molecules. Although APC mutations remain the most important driver of Wnt signalling in CRC , many Wnt components can modulate the signal output in spite of APC truncations.