RESUMO
Interactions between the cell and the extracellular matrix (ECM) are critical in controlling the fate and behaviour of cancer cells. Alterations in either the ECM or in cellular events affect this interaction. In this mini-review we give an overview of the role of cell-ECM interactions in cancer, with a particular focus on the reciprocal nature of the cell-ECM interactions and how this contributes to cancer progression.
Assuntos
Comunicação Celular , Fenômenos Fisiológicos Celulares , Matriz Extracelular/patologia , Neoplasias/patologia , Animais , HumanosRESUMO
A gene encoding a putrescine oxidase (PuORh, EC 1.4.3.10) was identified from the genome of Rhodococcus erythropolis NCIMB 11540. The gene was cloned in the pBAD vector and overexpressed at high levels in Escherichia coli. The purified enzyme was shown to be a soluble dimeric flavoprotein consisting of subunits of 50 kDa and contains non-covalently bound flavin adenine dinucleotide as a cofactor. From all substrates, the highest catalytic efficiency was found with putrescine (KM=8.2 microM, kcat=26 s(-1)). PuORh accepts longer polyamines, while short diamines and monoamines strongly inhibit activity. PuORh is a reasonably thermostable enzyme with t1/2 at 50 degrees C of 2 h. Based on the crystal structure of human monoamine oxidase B, we constructed a model structure of PuORh, which hinted to a crucial role of Glu324 for substrate binding. Mutation of this residue resulted in a drastic drop (five orders of magnitude) in catalytic efficiency. Interestingly, the mutant enzyme showed activity with monoamines, which are not accepted by wt-PuORh.
