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

• Verfasst von: Funke, Verena [VerfasserIn]
• Verfasst von: Lehmann-Koch, Judith [VerfasserIn]
• Verfasst von: Bickeböller, Michèle [VerfasserIn]
• Verfasst von: Benner, Axel [VerfasserIn]
• Verfasst von: Tagscherer, Katrin [VerfasserIn]
• Verfasst von: Grund, Kerstin [VerfasserIn]
• Verfasst von: Pfeifer, Marco [VerfasserIn]
• Verfasst von: Herpel, Esther [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Chang-Claude, Jenny [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Hoffmeister, Michael [VerfasserIn]
• Verfasst von: Roth, Wilfried [VerfasserIn]
• Titel: The PEA-15/PED protein regulates cellular survival and invasiveness in colorectal carcinomas
• Verf.angabe: 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
• E-Jahr: 2013
• Jahr: 28 July 2013
• Umfang: 10 S.
• Teil: volume:335
• Teil: year:2013
• Teil: number:2
• Teil: pages:431-440
• Teil: extent:10
• Fussnoten: Gesehen am 14.06.2021
• Titel Quelle: Enthalten in: Cancer letters
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1975
• Jahr Quelle: 2013
• Band/Heft Quelle: 335(2013), 2, Seite 431-440
• ISSN Quelle: 1872-7980
• DOI: doi:10.1016/j.canlet.2013.02.053
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Erscheint auch als : Druck-Ausgabe: Funke, Verena: The PEA-15/PED protein regulates cellular survival and invasiveness in colorectal carcinomas. - 2013
• Sach-SW: Apoptosis
• Sach-SW: Colorectal carcinoma
• Sach-SW: Invasiveness
• Sach-SW: PEA-15/PED
• Sach-SW: Proliferation
• K10plus-PPN: 176040361X

Abstract

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.