Vinculin activators target integrins from within the cell to increase melanoma sensitivity to chemotherapy.

ABSTRACT: Metastatic melanoma is an aggressive skin disease for which there are no effective therapies. Emerging evidence indicates that melanomas can be sensitized to chemotherapy by increasing integrin function. Current integrin therapies work by targeting the extracellular domain, resulting in complete gains or losses of integrin function that lead to mechanism-based toxicities. An attractive alternative approach is to target proteins, such as vinculin, that associate with the integrin cytoplasmic domains and regulate its ligand-binding properties. Here, we report that a novel reagent, denoted vinculin-activating peptide or VAP, increases integrin activity from within the cell, as measured by elevated (i) numbers of active integrins, (ii) adhesion of cells to extracellular matrix ligands, (iii) n

SUBMITTER: Nelson ES 

PROVIDER: S-EPMC3134390 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature