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Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis

Nature Reviews Molecular Cell Biology volume 4, pages 657–665 (2003)Cite this article

Abstract

In contrast to the aberrant control of proliferation, apoptosis, angiogenesis and lifespan, the cellular mechanisms that cause local invasion and metastasis of tumour cells are still poorly understood. New experimental approaches have identified different types of epithelial-plasticity changes in tumour cells towards fibroblastoid phenotypes as crucial events that occur during metastasis, and many molecules and signalling pathways cooperate to trigger these processes.

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Figure 1: Diversity of epithelial phenotypes.
Figure 2: Multiparameter analysis of epithelial-plasticity phenotypes in 3D collagen gel cultures.
Figure 3: Different Ras downstream signalling pathways contribute to distinct tumour phenotypes in vivo.
Figure 4: Signalling networks regulating carcinoma progression.

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Acknowledgements

The authors would like to thank N. Kraut and R. Foisner for critically reading the manuscript and G. Litos and A. Sommer for expert technical assistance. This work was supported by grants from the Fonds zur Förderung der Wissenschaftlichen Forschung and the Forschunapförderungsfonds der gewerblichen Wirtschaft.

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Author notes

  1. Stefan Grünert and Martin Jechlinger: These authors contributed equally to this paper.

Authors and Affiliations

  1. the Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria

    Stefan Grünert & Hartmut Beug

  2. the Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 62, New York, 10021, USA

    Martin Jechlinger

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  1. Stefan Grünert
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Correspondence to Stefan Grünert, Martin Jechlinger or Hartmut Beug.

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DATABASES

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α5 integrin

β4 integrin

BMPs

FGF

H-Ras

MAPK

MEK

PDGF

PI3K

Rac

Ras

Rho

Smads

TGF-β

Swiss-Prot

Bcl2

E-cadherin

EGF

ErbB2

HGF

Lef1

N-cadherin

PKB

Raf1

Smad2

Smad4

Smad6

Smad7

TNF-α

transforming growth factor α

vimentin

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Grünert, S., Jechlinger, M. & Beug, H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol 4, 657–665 (2003). https://doi.org/10.1038/nrm1175

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