APC and neoplasm: However, despite constitutive activation of Wnt/β-catenin signaling by mutant APC, additional regulation of the Wnt signaling pathway occurs in a spaciotemporal manner, so that bursts of intense Wnt/β-catenin signaling are observed during tumor progression; for example, signaling was found to occur at the invasive front of CRC associated with EMT [16] and during MET to establish the metastases at the secondary site [15].