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PMID: 22554795 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links.

Seminars in cancer biology ·Vol. 22 ·No. 5-6 ·2012-10-00 ·Pages 396-403

Scheel C, Weinberg RA

Abstract

The epithelial-mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by carcinoma cells. EMT programs are orchestrated by a set of pleiotropically acting transcription factors (TFs). The actions of these EMT-TFs enable the early steps of metastasis: local invasion and subsequent dissemination of carcinoma cells to distant sites. However, in most malignancies, the subsequent outgrowth of micrometastatic deposits into macroscopic metastases has the greatest impact on clinical progression. Such metastatic "colonization" reflects the ability of disseminated tumor cells to adapt to a foreign tissue microenvironment. The outgrowth of a metastasis is also thought to be associated with self-renewal, the defining cellular trait of cancer stem cells (CSCs), also termed tumor-initiating cells. Importantly, molecular links between EMT-TFs and self-renewal have emerged, suggesting that EMT programs play critical roles both early and late in the metastatic cascade. The genetic and epigenetic mechanisms that regulate the activation of EMT-TFs and the traits they induce are areas under intensive investigation. Such studies may provide new opportunities for therapeutic intervention and help to overcome tumor heterogeneity and therapeutic resistance.

MeSH Terms
Animals Epithelial-Mesenchymal Transition/genetics Humans Neoplasm Metastasis Neoplasms/genetics,metabolism,pathology Neoplastic Stem Cells/metabolism Transcription Factors/genetics,metabolism
Chemicals
Transcription Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Scheel Christina
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. scheel@wi.mit.edu
Weinberg Robert A
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Article Info
Journal
Seminars in cancer biology
Abbr.
Semin Cancer Biol
ISSN
1096-3650
DOI
10.1016/j.semcancer.2012.04.001
Email
scheel@wi.mit.edu
Published
2012-10-00
Epub
2012-00-23
Pages
396-403
Language
English
Region
England
NLM ID
9010218
PMCID
PMC6220425
Subset
IM
Grants
NCI NIH HHS · R01 CA125153 · United States
NIDCR NIH HHS · RC1 DE020817 · United States
NIDCR NIH HHS · DE020817 · United States
NCI NIH HHS · CA12515 · United States
External Links
PubMed source DOI: 10.1016/j.semcancer.2012.04.001 PMC Full Text View journal details
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