Smad6 suppresses TGF-β-induced growth inhibition in COLO-357 pancreatic cancer cells and is overexpressed in pancreatic cancer

Jörg Kleeff, Haruhisha Maruyama, Helmut Friess, Markus W. Büchler, Dean Falb, Murray Korc

Research output: Contribution to journalArticle

102 Scopus citations


Transforming growth factor (TGF)-β signaling is initiated by heterodimerization of TGF-β receptor type I (TβRI) and type II (TβRII). Subsequently, the signal is transduced via Smad proteins, which upon phosphorylation and heterodimerization translocate to the nucleus and regulate gene transcription. Smad6 functions as an intracellular antagonist of TGF-β signaling. In the present study we demonstrate that Smad6 is overexpressed in vivo in human pancreatic cancer cells. We also show that stable transfection of a full-length Smad6 construct into COLO-357 pancreatic cancer cells abrogates TGF-β1 induced growth inhibition, and leads to enhanced anchorage-independent growth. Thus, enhanced expression of the TGF-β signaling inhibitor Smad6 in pancreatic cancer may present a novel mechanism of TGF-β resistance, which might have the potential to enhance the transformed phenotype of human cancer cells.

Original languageEnglish (US)
Pages (from-to)268-273
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Feb 16 1999



  • Cancer
  • Pancreas
  • Smad6
  • TGF-β

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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