The signaling architecture defining self-renewal and lineage specification is maintained in colon cancer progression. Although genetic hits accumulate during progression (e.g. depicted as APC mutation in adenoma), signals defining self-renewal and lineage specification are orchestrated similarly between normal and cancerous tissues. On the left part of each progression step, stemness potential is defined by a gradient of Wnt signals (green, high (dark green) in normal stem cells and cancer stem cells and low (light green) in differentiated (tumor) cells). The right part of each progression step depicts the response to a specific morphogenic cue; in this case inhibition of Notch signaling promotes differentiation towards goblet cells (pink).