The PEA-15/PED protein regulates cellular survival and invasiveness in colorectal carcinomas
The PEA-15/PED (phosphoprotein enriched in astrocytes 15kD/phosphoprotein enriched in diabetes) protein is a multifunctional phosphoprotein involved in various signaling pathways which determine survival, proliferation, and migration of cancer cells. Here, we investigated the expression and cellular...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 July 2013
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| In: |
Cancer letters
Year: 2013, Volume: 335, Issue: 2, Pages: 431-440 |
| ISSN: | 1872-7980 |
| DOI: | 10.1016/j.canlet.2013.02.053 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.canlet.2013.02.053 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0304383513002164 
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| Author Notes: | Verena Funke, Judith Lehmann-Koch, Michèle Bickeböller, Axel Benner, Katrin E. Tagscherer, Kerstin Grund, Marco Pfeifer, Esther Herpel, Peter Schirmacher, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister, Wilfried Roth |
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| 520 | |a The PEA-15/PED (phosphoprotein enriched in astrocytes 15kD/phosphoprotein enriched in diabetes) protein is a multifunctional phosphoprotein involved in various signaling pathways which determine survival, proliferation, and migration of cancer cells. Here, we investigated the expression and cellular functions of PEA-15 in colorectal carcinoma (CRC). PEA-15 is expressed in the majority of human CRC, predominantly in well differentiated tumor areas. A tissue microarray analysis of 1262 human CRC specimens from the DACHS study showed that PEA-15 expression is significantly associated with a low pT stadium as defined by limited invasion into the bowel wall. Moreover, patients with PEA-15-positive CRC exhibited a significantly longer tumor-specific survival time. To investigate the functional relevance of PEA-15 expression on a cellular level, we over-expressed PEA-15 in several CRC cell lines. Increased expression of PEA-15 resulted in a strong inhibition of clonogenicity, proliferation, and invasiveness of CRC cells. These effects were associated with a PEA-15-dependent down-regulation of integrin αvβ5 as well as with elevated levels of the phosphorylated MAP kinase ERK1/2. Moreover, expression of PEA-15 resulted in significant protection from cell death induced by cytotoxic drugs (5-FU, cisplatin), by the death ligand TRAIL, or by serum withdrawal. In conclusion, the PEA-15 protein regulates invasiveness, proliferation, and apoptosis resistance in CRC cells. PEA-15 might play an important role in chemoresistance, progression and metastasis in CRC. | ||
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Colorectal carcinoma | |
| 650 | 4 | |a Invasiveness | |
| 650 | 4 | |a PEA-15/PED | |
| 650 | 4 | |a Proliferation | |
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