RESUMEN

Tissue transglutaminase (TG2) is a multifunctional enzyme involved in the cross-linking of extracellular matrix proteins, formation of complexes with fibronectin (FN) and integrins, and GTP hydrolysis. TG2 is activated in several pathological conditions, including cancer. We recently described a novel series of ligands that bind to TG2 and inhibit its interaction with FN. Because TG2 acts via multiple mechanisms, we set out to pursue a targeted protein degradation strategy to abolish TG2's myriad functions. Here, we report the synthesis and characterization of a series of VHL-based degraders that reduce TG2 in ovarian cancer cells in a proteasome-dependent manner. Degradation of TG2 resulted in significantly reduced cancer cell adhesion and migration in vitro in scratch-wound and migration assays. These results strongly indicate that further development of more potent and in vivo efficient TG2 degraders could be a new strategy for reducing the dissemination of ovarian and other cancers.

Asunto(s)

Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas , Femenino , Humanos , Quimera Dirigida a la Proteólisis , Proteínas de Unión al GTP/metabolismo , Adhesión Celular

RESUMEN

The focusing field effect excited by the cavity mode has a positive coupling effect with the metal localized surface plasmon resonance (LSPR) effect, which can stimulate a stronger local electromagnetic field. Therefore, we combined the self-organizing process for component and array manufacturing with imprinting technology to construct a cheap and reproducible flexible polyvinyl alcohol (PVA) nanocavity array decorating with the silver nanoparticles (Ag NPs). The distribution of the local electromagnetic field was simulated theoretically, and the surface-enhanced Raman scattering (SERS) performance of the substrate was evaluated experimentally. The substrate shows excellent mechanical stability in bending experiments. It was proved theoretically and experimentally that the substrate still provides a stable signal when the excited light is incident from different angles. This flexible substrate can achieve low-cost, highly sensitive, uniform and conducive SERS detection, especially in situ detection, which shows a promising application prospect in food safety and biomedicine.