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

69 Citations (Scopus)

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

Fingerprint

Epithelial-Mesenchymal Transition
Transforming Growth Factors
Cell Cycle
Apoptosis
G1 Phase
S Phase
Biological Phenomena
Protein Kinase Inhibitors
Caspases
RNA Interference
Embryonic Development
Fibrosis
Epithelial Cells
Phosphorylation
protein kinase D
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism. / Yang, Y.; Pan, X.; Lei, W.; Wang, J.; Song, J.

In: Oncogene, Vol. 25, No. 55, 23.11.2006, p. 7235-7244.

Research output: Contribution to journalArticle

@article{df7d7c512ebb498d8989f50d605b2be5,
title = "Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism",
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.",
keywords = "Apoptosis, Cell cycle, EMT, PKD, Signaling, TGF-β",
author = "Y. Yang and X. Pan and W. Lei and J. Wang and J. Song",
year = "2006",
month = "11",
day = "23",
doi = "10.1038/sj.onc.1209712",
language = "English (US)",
volume = "25",
pages = "7235--7244",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "55",

}

TY - JOUR

T1 - Transforming growth factor-β1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism

AU - Yang, Y.

AU - Pan, X.

AU - Lei, W.

AU - Wang, J.

AU - Song, J.

PY - 2006/11/23

Y1 - 2006/11/23

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cell cycle

KW - EMT

KW - PKD

KW - Signaling

KW - TGF-β

UR - http://www.scopus.com/inward/record.url?scp=33751315728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751315728&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1209712

DO - 10.1038/sj.onc.1209712

M3 - Article

C2 - 16799646

AN - SCOPUS:33751315728

VL - 25

SP - 7235

EP - 7244

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 55

ER -