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Lung Cancer Metastasis pp 65–92Cite as

Epithelial–Mesenchymal Transition as a Mechanism of Metastasis

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Abstract

Mammalian embryonic cells form adhering cell sheets interconnected via various intercellular junctional complexes. Gastrulation and later stages of histo- and organogenesis depend on changes in developmental stage, such as epithelial–mesenchymal transition (EMT), whereby adherent cells disintegrate their intercellular contacts, organize their motility apparatus, and move to new locations in the developing body. EMT generates transitory mesenchymal cells, which can differentiate into myofibroblasts or pericytes (in the case of endothelial–mesenchymal transition (EndMT)), or feed the progenitor pools of cell lineages (e.g., blood, muscle, bone, adipose, and neuronal). EMT is guided by cues from extracellular signaling factors including mitogens, transforming growth factor β, Notch, and Wnt. The signaling molecules can cooperate or act sequentially to initiate transcriptional programs that involve many transcriptional regulators. Changes in gene expression lead to a reprogramming of epithelial protein components and the generation of the mesenchymal progenitor stage. EMT can also contribute to the progression of cancer, when the same growth factor pathways reawaken embryonic transcriptional programs otherwise silenced in adult life. Induction of cancer cell EMT generates rare transitory mesenchymal cells that support tumor growth, remodel the tumor microenvironment, and facilitate tissue invasiveness and metastasis. In that sense, cancer cells undergoing EMT have some of the capacities that one would expect from the so-called “tumor-initiating cells.” This makes EMT an attractive problem for medical research with new therapeutic implications.

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Acknowledgments

Due to space limitations, only selected literature is cited. Funding of the authors’ work is provided by the Ludwig Institute for Cancer Research, the Atlantic Philanthropies/Ludwig Institute for Cancer Research Clinical Discovery Program, the Swedish Cancer Society, the Swedish Research Council and the Marie Curie Research Training Network (RTN) “EpiPlastCarcinoma” under the European Union FP6 program. We thank Carl-Henrik Heldin for his continuous support and all other members of the TGFβ signaling group for their contributions to the scientific work emanating from our laboratory.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, SE-751 24, Uppsala, Sweden

    Katia Savary, Stefan Termén & Sylvie Thuault

  2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, 48109-2200, Ann Arbor, MI, USA

    Venkateshwar Keshamouni Ph.D.

  3. Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Uppsala, Sweden

    Aristidis Moustakas

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  1. Katia Savary
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Correspondence to Aristidis Moustakas .

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  1. Dept. Internal Medicine, University of Michigan Health System, Zina Pitcher Place 109, Ann Arbor, 48109-2200, U.S.A.

    Venkateshwar Keshamouni

  2. Dept. Internal Medicine, University of Michigan, E. Medical Center Drive 1500, Ann Arbor, 48109, U.S.A.

    Douglas Arenberg

  3. Dept. Internal Medicine, University of Michigan, E. Medical Center Drive 1500, Ann Arbor, 48109, U.S.A.

    Gregory Kalemkerian

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Savary, K., Termén, S., Thuault, S., Keshamouni, V., Moustakas, A. (2009). Epithelial–Mesenchymal Transition as a Mechanism of Metastasis. In: Keshamouni, V., Arenberg, D., Kalemkerian, G. (eds) Lung Cancer Metastasis. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0772-1_4

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