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PLoS One. 2013 Jun 27;8(6):e67109. doi: 10.1371/journal.pone.0067109. Print 2013.

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.

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Department of Emergency and Organ Transplantation, Section of Internal Medicine Allergology and Immunology, University of Bari Medical School, Bari, Italy.

Erratum in

  • PLoS One. 2013;8(7). doi:10.1371/annotation/c943a596-3965-4a5b-a27c-55c16685ea32. Peidrò, Fernando Juan [corrected to Fernando, Joan].
  • PLoS One. 2014;9(6):e100604.


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.

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