A Four Amino Acid Intracellular Motif of VISTA Blocks Growth Receptor Signaling in Cancer Cells to Induce Tumor Suppression.

ABSTRACT: V-domain immunoglobulin suppressor of T-cell activation (VISTA, VSIR) is a key immune checkpoint receptor under investigation as a target for cancer immunotherapy. However, a better understanding of the signaling mechanisms of VISTA is needed to optimize the therapeutic potential. In this study, we identified a conserved four amino acid (NPGF) intracellular motif in VISTA that suppresses cell proliferation by constraining cell-intrinsic growth receptor signaling. A class of triple-negative breast cancers (TNBC) with high VISTA expression and low proliferative index was identified and characterized. The NPGF motif bound to the adapter protein NUMB and recruited Rab11 endosomal recycling machinery. The NPGF motif sequestered NUMB at endosomes, which interfered with EGFR trafficking and signa

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12317733 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature