Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23826206.
- Also identified by DOI 10.1371/journal.pone.0067109 and PMC identifier 3694933.
- 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
We investigated blocking the TGF-β signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-βRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-βRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-β receptor cycling in cancer cells.
Medical subject headings
- Antineoplastic Agents
- Carcinoma, Hepatocellular
- Homeodomain Proteins
- Liver Neoplasms
- Protein Serine-Threonine Kinases
- Pyrazoles
- Quinolines
- Receptors, Transforming Growth Factor beta
- Transcription Factors