RESUMO
Most solid cancer-related deaths result from metastasis, a multistep process in which cancer cells exit the primary site, intravasate into the bloodstream, extravasate, and colonize distant organs. Colonization is facilitated by clonal selection and the high phenotypic plasticity of cancer cells that creates reversible switching of cellular states. Cancer cell plasticity leads to intratumor heterogeneity and fitness, yielding cells with molecular and cellular programs that facilitate survival and colonization. While cancer cell plasticity is sometimes limited to the process of epithelial-to-mesenchymal transition (EMT), recent studies have broadened its definition. Plasticity arises from both cell-intrinsic and cell-extrinsic factors and is a major obstacle to efficacious anti-cancer therapies. Here, we discuss the multifaceted notion of cancer cell plasticity associated with metastatic colonization.
Assuntos
Neoplasias , Adaptação Fisiológica , Plasticidade Celular , Transição Epitelial-Mesenquimal , Humanos , Metástase Neoplásica , Neoplasias/patologiaRESUMO
We report the first method of enzyme protection enabling the production of partially shielded enzymes capable of processing substrates as large as proteins. We show that partially shielded sortase retains its transpeptidase activity and can perform bioconjugation reactions on antibodies. Moreover, a partially shielded trypsin is shown to outperform its soluble counterpart in terms of proteolytic kinetics. Remarkably, partial enzyme shielding results in a drastic increase in temporal stability of the enzyme.
Assuntos
Aminoaciltransferases/metabolismo , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/metabolismo , Aminoaciltransferases/química , Proteínas de Bactérias/química , Cisteína Endopeptidases/química , Cinética , Tamanho da Partícula , Proteólise , Staphylococcus aureus/enzimologia , Especificidade por Substrato , Propriedades de SuperfícieRESUMO
Transaminases are enzymes capable of stereoselective reductive amination; they are of great interest in the production of chiral building blocks. However, the use of this class of enzymes in industrial processes is often hindered by their limited stability under operational conditions. Herein, we demonstrate that a transaminase enzyme from Aspergillus terreus can be immobilized at the surface of silica nanoparticles and protected in an organosilica shell of controlled thickness. The so-protected enzyme displays a high biocatalytic activity, and additionally provides the possibility to be retained in a reactor system for continuous operation and to be recycled.