Schmidt, Jennifer and Bosserhoff, Anja-Katrin (2009) Processing of MIA protein during melanoma cell migration. INTERNATIONAL JOURNAL OF CANCER, 125 (7). pp. 1587-1594. ISSN 0020-7136,
Full text not available from this repository. (Request a copy)Abstract
MIA (melanoma inhibitory activity) protein, identified as a small 11 kDa protein highly expressed and secreted by malignant melanoma cells, plays an important functional role in melanoma development, progression and tumor cell invasion. Recent data describe a direct interaction of MIA protein with cell adhesion receptors integrin alpha(4)beta(1) and integrin alpha(5)beta(1) and extracellular matrix molecules. By modulating integrin activity MIA protein mediates detachment of melanoma cells from surrounding structures resulting in enhanced invasive and migratory potential. However, until today a detailed understanding of the processes of MIA function is missing. In this study, we show that after binding of MIA protein to integrin alpha(5)beta(1), MIA protein is internalized together with this cell adhesion receptor at the cell rear. 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. 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. (C) 2009 UICC
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INHIBITORY ACTIVITY PROTEIN; MALIGNANT-MELANOMA; INTEGRIN TRAFFICKING; ENDOCYTIC RECEPTOR; FIBRONECTIN; VITRONECTIN; METASTASIS; MATRIX; DOMAIN; INTERNALIZATION; melanoma; MIA; endocytosis; migration; integrin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Sep 2020 05:15 |
| Last Modified: | 04 Sep 2020 05:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28347 |
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