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HER2 in stemness and epithelial–mesenchymal plasticity of breast cancer

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Abstract

Breast cancer had been the first non-hematologic malignancy where sub-types based on molecular characterization had entered clinical practice. HER2 over-expression, due to either gene amplification or protein up-regulation, defines one of these sub-types and is clinically exploited by addition of HER2-targeted treatments to the regimens of treatment. Nevertheless, in many occasions HER2-positive cancers are resistant or become refractory to these therapies. Several mechanisms, such as activation of alternative pathways or loss of expression of the receptor in cancer cells, have been proposed as the cause of these therapeutic failures. Cancer stem cells (CSCs, alternatively called tumor-initiating cells) comprise a small percentage of the tumor cells, but are capable of reconstituting and propagating tumors due to their superior intrinsic capacity for regeneration, survival and resistance to therapies. CSCs possess circuits enabling epigenetic plasticity which endow them with the ability to alternate between epithelial and mesenchymal states. This paper will discuss the expression and regulation of HER2 in CSCs of the different sub-types of breast cancer and relationships of the receptor with both the circuits of stemness and epithelial–mesenchymal plasticity. Therapeutic repercussions of the relationship of HER2-initiated signaling with stemness networks will also be proposed.

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  1. Algoma District Cancer Program, Sault Area Hospital, 750 Great Northern Road, Sault Ste. Marie, ON, P6B 0A8, Canada

    I. A. Voutsadakis

  2. Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada

    I. A. Voutsadakis

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Voutsadakis, I.A. HER2 in stemness and epithelial–mesenchymal plasticity of breast cancer. Clin Transl Oncol 21, 539–555 (2019). https://doi.org/10.1007/s12094-018-1961-x

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