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Processing of MIA protein during melanoma cell migration
Schmidt J et al. - In a study to gain a detailed understanding of the processes of melanoma inhibitory activity (MIA) protein function, it was found that as MIA protein has a major contribution to the aggressive characteristics of malignant melanoma in particular to formation of metastasis, it is important to elucidate the MIA functional mechanism in tumor cells to find novel therapeutic strategies in the fight against skin cancer.

Methods
  • In this study, it was shown that after binding of MIA protein to integrin α5β1, MIA protein is internalized together with this cell adhesion receptor at the cell rear.

Results
  • This mechanism enables tumor cells to migrate in a defined direction as appropriate for invasion processes.
  • Treatment of melanoma cells with PKC-inhibitors strongly reduced internalization of MIA protein.
  • Endocytosis is followed by dissociation of MIA-integrin complexes.
  • In acidic vesicles MIA protein is degraded while integrins are recycled.
  • Treatment of melanoma cells with MIA inhibitory peptides almost completely blocked the MIA protein uptake into cells.
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