FAT1 and neoplasm: Of particular significance, FAT1, a prototypical cadherin superfamily member, exhibited the most pronounced transcriptional downregulation in mLECs grown on tumor-mimetic stiff substrates (10 kPa) relative to physiological soft matrices (1.5 kPa), with subsequent confirmation at the protein level in both mLECs and hLECs (Figures 3F,G; Supplementary Figure S1H, I).