D-tryptophan triggered epithelial-mesenchymal transition by activating TGF-β signaling pathway

D-tryptophan is a special kind of nonprotein amino acid showing multiple physiological functions, but the detailed mechanisms arc not fully revealed, impairing its further development and applications. This work was to investigate D-tryptophan physiological function and demonstrate the underlying mechanisms. D-tryptophan suppressed HaCaT cell proliferation but increased cell migration. Specifically, D-tryptophan decreased E-cadherin and increased Snail, Twist, and Slug expression, resulting in the development of an epithelial-mesenchymal transitions (EMT) phenomenon. Moreover, D-tryptophan promoted the expression of transforming growth factor-beta (TGF-beta) 1, and Smad4 knockout damages D-tryptophan's ability. These results indicated that D-tryptophan stimulated HaCaT cells to produce TGF-beta 1 and thus activated the TGF-beta/Samd pathway, resulting in the triggering of EMT. This study revealed the molecular mechanisms of D-tryptophan activity, provided D-tryptophan as a potential approach for cancer treatment, wound healing, organ development and other relevant applications. (C) 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.