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The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer Therapies

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

During cancer progression, some cells within the primary tumor may reactivate a latent embryonic program known as epithelial-to-mesenchymal transition (EMT). Through EMT, transformed epithelial cells can acquire the mesenchymal traits that seem to facilitate metastasis. Indeed, there is accumulating evidence that EMT and mesenchymal-related gene expression are associated with aggressive breast cancer subtypes and poor clinical outcome in breast cancer patients. More recently, the EMT program was shown to endow normal and transformed mammary epithelial cells with stem cell properties, including the ability to self-renew and efficiently initiate tumors. This link between EMT and stem cells may have numerous implications in the progression of breast tumors. The EMT process may facilitate the generation of cancer cells with the mesenchymal traits needed for dissemination as well as the self-renewal properties needed for initiation of secondary tumors. Breast cancer stem cells are resistant to many conventional cancer therapies, which can promote tumor relapse. Therefore, the generation of cancer stem cells by EMT may promote the development of refractory and resistant breast tumors. The purpose of this review is to summarize the findings related to EMT and stem cells in cancer progression and therapy resistance.

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Abbreviations

AKT:

v-akt murine thyoma viral oncogene homolog 1

ALDH:

Aldehyde dehydrogenase

CSC:

Cancer stem cell

CXCR4:

Chemokine (C-X-C motif) receptor 4

EMT:

Epithelial-to-mesenchymal transition

EGFR:

Epidermal growth factor receptor

ESA:

Epithelial-specific antigen

FN:

Fibronectin

HER2:

Human epidermal growth factor receptor 2 (also known as ERBB2)

HSC:

Hematopoietic stem cell

IBC:

Inflammatory breast cancer

MAPK:

Mitogen-activated protein kinase

MaSC:

Mammary stem cell

MBC:

Metaplastic breast cancer

MET:

Mesenchymal-to-epithelial transition

Sca-1:

Stem cell antigen-1

SMA:

Smooth-muscle actin

TCF4:

Transcription factor 4

TGF-β:

Transforming growth factor beta

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Acknowledgements

We apologize to the researchers whose work could not be included in this review because of space limitation. We thank Robert A. Weinberg for his previous and continued support. We also thank Karen Phillips from the Department of Scientific Publications at The University of Texas M. D. Anderson Cancer Center and Lovepreet Mann for critical reading of the manuscript. S.A.M.’s laboratory is supported by the Jimmy V Foundation as well as by The University of Texas M. D. Anderson Cancer Center Research Trust Fund.

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  1. Department of Molecular Pathology, Unit 951, The University of Texas M. D. Anderson Cancer Center, 2SCR4.2030, 7435 Fannin St., Houston, TX, 77054, USA

    Brett G. Hollier, Kurt Evans & Sendurai A. Mani

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Hollier, B.G., Evans, K. & Mani, S.A. The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer Therapies. J Mammary Gland Biol Neoplasia 14, 29–43 (2009). https://doi.org/10.1007/s10911-009-9110-3

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