Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26114631.
- Also identified by DOI 10.1371/journal.pone.0131506 and PMC identifier 4484253.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Colorectal Neoplasms
- Growth Differentiation Factor 15
- Protein Serine-Threonine Kinases
- Receptors, Transforming Growth Factor beta