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The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells

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Cancer Stem Cells in Solid Tumors

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

The epithelial-to-mesenchymal transition (EMT) is a developmental process which is reactivated during carcinoma progression, providing tumor cells with enhanced migratory properties, the capacity to invade the stroma, and the ability to metastasize. Tumor cells undergoing EMT also acquire stem cell characteristics, suggesting that there is crosstalk between pathways promoting EMT and self-renewal, and that the EMT process contributes to the generation of cancer stem cells. This chapter summarizes findings pointing to molecular links between EMT and cancer stem cells. The focus is crosstalk between signaling by the transforming growth factor-beta (TGF-β)/Smad pathway, a major inducer of EMT, and stem cell pathways including Wnt, Ras, Hedgehog, and Notch. Finally, the existence of EMT/stem cell niches in tumors where cooperative signaling between TGF-β and self-renewal pathways is activated is discussed.

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Abbreviations

ALDH1:

Aldehyde dehydrogenase 1

AP-1:

Activator protein-1

APC:

Adenomatous polyposis coli

bHLH:

Basic helix-loop-helix

CAR:

Coxsackie- and adenovirus receptor

CD:

Cluster of differentiation

EMT:

Epithelial-to-mesenchymal transition

EpR:

Epithelial repressors

EPSC:

EMT promoting Smad complexes

ERK:

Extracellular signal-regulated kinase

ERα:

Estrogen receptor-α

GSK-3β:

Glycogen synthase kinase-3beta

HIF-1α:

Hypoxia-inducible factor 1 alpha

HMGA2:

High mobility group A2

LDL:

Low density lipoprotein

LEF:

Lymphoid enhancer factor

MAPK:

Mitogen-activated protein kinase

MeA:

Mesenchymal activators

MMP:

Matrix metalloproteinase

NF B:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PAI-1:

Plasminogen activator inhibitor 1

PI3K:

Phosphoinositol-3-kinase

RTK:

Receptor tyrosine kinase

Sp1:

Specificity protein 1

TCF:

T cell factor

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

α-SMA:

Alpha smooth muscle actin

β-Cat:

Beta Catenin

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  1. Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

    Jonas Fuxe

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  1. Jonas Fuxe
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Correspondence to Jonas Fuxe .

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  1. Dept. Oncology & Anatomy & Cell Biology, University of Western Ontario, Commissioners Road East 790, London, N6A 4L6, Ontario, Canada

    Alison L. Allan

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Fuxe, J. (2011). The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells. In: Allan, A. (eds) Cancer Stem Cells in Solid Tumors. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-246-5_14

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