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Migrating cancer stem cells — an integrated concept of malignant tumour progression

Abstract

The dissemination of tumour cells is the prerequisite of metastases and is correlated with a loss of epithelial differentiation and the acquisition of a migratory phenotype, a hallmark of malignant tumour progression. A stepwise, irreversible accumulation of genetic alterations is considered to be the responsible driving force. But strikingly, metastases of most carcinomas recapitulate the organization of their primary tumours. Although current models explain distinct and important aspects of carcinogenesis, each alone can not explain the sum of the cellular changes apparent in human cancer progression. We suggest an extended, integrated model that is consistent with all aspects of human tumour progression — the 'migrating cancer stem (MCS)-cell' concept.

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Figure 1: Phenotype and β-catenin expression pattern in colorectal cancer (primary carcinoma) and liver metastasis.
Figure 2: Expression of stem cell- and EMT-markers in colorectal cancer progression.
Figure 3: Schematic of dynamic tumour progression.
Figure 4: The migrating cancer stem (MCS)-cell concept.

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Acknowledgements

The authors would like to acknowledge funding from the German Research Council (DFG), the National Genomic Research Network (NGFN), the Deutsche Krebshilfe and the Sander-Stiftung.

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Correspondence to Thomas Brabletz.

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Related links

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DATABASES

Entrez Gene

APC

CCND1

CDKN2A

EGF

HGF

ILK

L1CAM

LAMC2

SIP1

SLUG

SNAI1L1

TCF4

TCF8

TWIST1

National Cancer Institute

breast cancer

colorectal cancer

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Brabletz, T., Jung, A., Spaderna, S. et al. Migrating cancer stem cells — an integrated concept of malignant tumour progression. Nat Rev Cancer 5, 744–749 (2005). https://doi.org/10.1038/nrc1694

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