Conformation-dependent binding of a Tetrastatin peptide to α_vβ₃ integrin decreases melanoma progression through FAK/PI₃K/Akt pathway inhibition.

ABSTRACT: Tetrastatin, a 230 amino acid sequence from collagen IV, was previously demonstrated to inhibit melanoma progression. In the present paper, we identified the minimal active sequence (QKISRCQVCVKYS: QS-13) that reproduced the anti-tumor effects of whole Tetrastatin in vivo and in vitro on melanoma cell proliferation, migration and invasion. We demonstrated that QS-13 binds to SK-MEL-28 melanoma cells through the α_vβ₃ integrin using blocking antibody and β3 integrin subunit siRNAs strategies. Relevant QS-13 conformations were extracted from molecular dynamics simulations and their interactions with α_Vβ₃ integrin were analyzed by docking experiments to determine the binding areas and the QS-13 amino acids crucial for the binding. The in silico resul

SUBMITTER: Lambert E 

PROVIDER: S-EPMC6026150 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature