title: Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells.
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.
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Cancer Early Detection, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Cancer Early Detection, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Fabia
authors.initials: F
authors.lastname: Fricke
authors.affiliation: Functional Proteome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Warnken
authors.affiliation: Functional Proteome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Schnölzer
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Cancer Early Detection, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kopitz
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Cancer Early Detection, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gebert
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055436:Growth Differentiation Factor 15 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051785:Smad Proteins / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II