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The PEA-15/PED protein regulates cellular survival and invasiveness in colorectal carcinomas

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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: Funke, Verena (Author) , Lehmann-Koch, Judith (Author) , Bickeböller, Michèle (Author) , Benner, Axel (Author) , Tagscherer, Katrin (Author) , Grund, Kerstin (Author) , Pfeifer, Marco (Author) , Herpel, Esther (Author) , Schirmacher, Peter (Author) , Chang-Claude, Jenny (Author) , Brenner, Hermann (Author) , Hoffmeister, Michael (Author) , Roth, Wilfried (Author)
Format: Article (Journal)
Language:English
Published: 28 July 2013
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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Summary: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.
Item Description:Gesehen am 14.06.2021
Physical Description:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2013.02.053

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