Reconstitution of TGFBR2-mediated signaling causes upregulation of GDF-15 in HCT116 colorectal cancer cells

• Verfasst von: Lee, Jennifer [VerfasserIn]
• Verfasst von: Fricke, Fabia [VerfasserIn]
• Verfasst von: Kopitz, Jürgen [VerfasserIn]
• Verfasst von: Gebert, Johannes [VerfasserIn]
• Titel: Reconstitution of TGFBR2-mediated signaling causes upregulation of GDF-15 in HCT116 colorectal cancer cells
• Verf.angabe: Jennifer Lee, Fabia Fricke, Uwe Warnken, Martina Schnölzer, Jürgen Kopitz, Johannes Gebert
• E-Jahr: 2015
• Jahr: 26 June 2015
• Fussnoten: Gesehen am 11.04.2015
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2015
• Band/Heft Quelle: 10(2015,6) Artikel-Nummer e0131506, 13 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0131506
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1556514824

Abstract

Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal cancer model cell line, we identified 21 de novo synthesized proteins differentially expressed upon reconstituted TGFBR2 expression. One candidate gene, the TGF-ß family member Growth differentiation factor-15 (GDF-15), exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels. As a new TGFBR2 target gene it may provide a link between the TGF-ß branch and the BMP/GDF branch of SMAD-mediated signaling.