Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism

Y. Yang, X. Pan, W. Lei, J. Wang, J. Song

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Apoptosis and epithelial-to-mesenchymal transition (EMT) have been implicated in a variety of biological processes, such as embryonic development, fibrosis and tumor progression. Transforming growth factor-β (TGF-β) can induce simultaneously both EMT and apoptotic response of epithelial cells. However, the underlying mechanism of these biological events remains not well understood. In the present study, we show that TGF-β1 induces apoptosis and EMT in AML-12 cells in a cell cycle-related manner, in which apoptosis and EMT took place at G2/M and G1/S phases, respectively. TGF-β1-induced apoptosis was correlated with different extent of caspase activation at different cell cycle phases. Interestingly, increased phosphorylation of protein kinase D (PKD) can be observed in G1/S phase in response to TGF-β1, and inhibition of PKD by inhibitor or by small interference RNA blocked EMT but not apoptosis. Our data suggest a previously unrecognized role of cell cycle state in the regulation of TGF-β-induced EMT and apoptosis, and demonstrate that PKD is involved in the TGF-β1-induced EMT.

Original languageEnglish (US)
Pages (from-to)7235-7244
Number of pages10
JournalOncogene
Volume25
Issue number55
DOIs
StatePublished - Nov 23 2006

Keywords

  • Apoptosis
  • Cell cycle
  • EMT
  • PKD
  • Signaling
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism'. Together they form a unique fingerprint.

  • Cite this