Among them, the lack of active canonical and non-canonical transforming growth factor β (TGFβ) signaling is key to explaining the inverted apical-out polarity orientation of 3D matrix-embedded CRC clusters both in vitro and in host tissue following mouse xenografting (Canet-Jourdan et al., 2022; Zajac et al., 2018). This evidence concerns the gene TGFB1 and colorectal carcinoma.