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Cell Polarity in Motion: Redefining Mammary Tissue Organization Through EMT and Cell Polarity Transitions

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

Abstract

Epithelial to mesenchymal transition (EMT) and its reversion via mesenchymal to epithelial transition (MET), represent a stepwise cycle of epithelial plasticity that allows for normal tissue remodelling and diversification during development. In particular, epithelial-mesenchymal plasticity is central to many aspects of mammary development and has been proposed to be a key process in breast cancer progression. Such epithelial-mesenchymal plasticity requires complex cellular reprogramming to orchestrate a change in cell shape to an alternate morphology more conducive to migration. During this process, epithelial characteristics, including apical-basal polarity and specialised cell-cell junctions are lost and mesenchymal properties, such as a front-rear polarity associated with weak cell-cell contacts, increased motility, resistance to apoptosis and invasiveness are gained. The ability of epithelial cells to undergo transitions through cell polarity states is a central feature of epithelial-mesenchymal plasticity. These cell polarity states comprise a set of distinct asymmetric distributions of cellular constituents that are fashioned to allow specialized cellular functions, such as the regulated homeostasis of molecules across epithelial barriers, cell migration or cell diversification via asymmetric cell divisions. Each polarity state is engineered using a molecular toolbox that is highly conserved between organisms and cell types which can direct the initiation, establishment and continued maintenance of each asymmetry. Here we discuss how EMT pathways target cell polarity mediators, and how this EMT-dependent change in polarity states impact on the various stages of breast cancer. Emerging evidence places cell polarity at the interface of proliferation and morphology control and as such the changing dynamics within polarity networks play a critical role in normal mammary gland development and breast cancer progression.

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Abbreviations

EMT:

Epithelial-mesenchymal transition

AB:

Apical-basal polarity

FR:

Front-rear polarity

PIP2 :

Phosphatidylinositol 4,5-bisphosphate

PIP3 :

Phosphatidylinositol 3,4,5-trisphosphate

TEB:

Terminal end bud

MDCK:

Madin-Darby canine kidney cells

MTOC:

Microtubule organising center

ECM:

Extracellular matrix

ACD:

Asymmetric cell division

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Acknowledgements

The authors would like to acknowledge Helen Pearson, Andreas Moeller and Robin Anderson for helpful discussions and comments during the writing of this manuscript. POH was supported by a Career Development Award from the Australian NHMRC, RG by an Australian Postgraduate Award and IE by a Postgraduate Cancer Research Scholarship from the Cancer Council Victoria. This work was supported by grants from the Australian NHMRC, Association for International Cancer Research UK and Cancer Council Victoria.

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Authors and Affiliations

  1. Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Center, East Melbourne, VIC, 3002, Australia

    Nathan J. Godde, Ryan C. Galea, Imogen A. Elsum & Patrick O. Humbert

  2. Department of Molecular Biology and Biochemistry, University of Melbourne, Parkville, VIC, 3052, Australia

    Ryan C. Galea, Imogen A. Elsum & Patrick O. Humbert

  3. Department of Pathology, University of Melbourne, Parkville, VIC, 3052, Australia

    Patrick O. Humbert

  4. Cell Cycle and Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Melbourne, VIC, 8006, Australia

    Patrick O. Humbert

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  1. Nathan J. Godde
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  2. Ryan C. Galea
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Correspondence to Patrick O. Humbert.

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Godde, N.J., Galea, R.C., Elsum, I.A. et al. Cell Polarity in Motion: Redefining Mammary Tissue Organization Through EMT and Cell Polarity Transitions. J Mammary Gland Biol Neoplasia 15, 149–168 (2010). https://doi.org/10.1007/s10911-010-9180-2

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  • DOI: https://doi.org/10.1007/s10911-010-9180-2

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