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Wnt Signaling, Stem Cells, and the Cellular Origin of Breast Cancer

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Abstract

The breast epithelium comprises cells at different stages of differentiation, including stem cells, progenitor cells, and more differentiated epithelial and myoepithelial cells. Wnt signaling plays a critical role in regulating stem/progenitor cells in the mammary gland as well as other tissue compartments. Furthermore, there is strong evidence suggesting that aberrant activation of Wnt signaling induces mammary tumors from stem/progenitor cells, and that Wnt exerts its oncogenic effects through LRP5/6-mediated activation of β-catenin and mTOR pathways. Recent studies using avian retrovirus-mediated introduction of oncogenes into a small subset of somatic mammary cells suggest that polyoma middle T antigen (PyMT) may also preferentially transform stem/progenitor cells. These observations suggest that stem/progenitor cells in the mammary gland may be especially susceptible to oncogenic transformation. Whether more differentiated cells may also be transformed by particular oncogenes is actively debated; it is presently unclear whether stem cells or differentiated mammary cells are more susceptible to transformation by individual oncogenes. Better stem cell and progenitor cell markers as well as the ability to specifically target oncogenes into different mammary cell types will be needed to determine the spectrum of oncogene transformation for stem cells versus more differentiated cells.

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Abbreviations

LRP:

low-density lipoprotein receptor-related protein

mTOR:

mammalian target of rapamycin

FRP:

Frizzled-related protein

tva:

tumor virus A

MMTV:

mouse mammary tumor virus

WAP:

whey acidic protein

PyMT:

polyoma middle T antigen

SMA:

smooth muscle actin

RCASBP(A)/RCAS:

replication-competent, ALV-LTR, splice acceptor, Bryan-RSV pol, subgroup A

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Acknowledgments

We thank Dr. Gary Chamness and David Nadziejka for the assistance in the preparation of this manuscript. This work was supported in part by funds from the National Institutes of Health R01 CA113869 (to YL) and Project 5 of MMHCC U01 CA084243-07 (to YL; U01 PI: Dr. Jeffrey Rosen), from the USAMRMC BC030755 (to YL), and from the Van Andel Research Institute (BOW).

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Authors and Affiliations

  1. Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI, 49503, USA

    Charlotta Lindvall & Bart O. Williams

  2. Breast Center Baylor College of Medicine, BCM600, One Baylor Plaza, Houston, TX, 77030, USA

    Wen Bu & Yi Li

  3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA

    Yi Li

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  1. Charlotta Lindvall
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  2. Wen Bu
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Correspondence to Yi Li.

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Lindvall, C., Bu, W., Williams, B.O. et al. Wnt Signaling, Stem Cells, and the Cellular Origin of Breast Cancer. Stem Cell Rev 3, 157–168 (2007). https://doi.org/10.1007/s12015-007-0025-3

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