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MUC1-mediated motility in breast cancer: a review highlighting the role of the MUC1/ICAM-1/Src signaling triad

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Abstract

Breast cancer is the most common cancer in women with the leading cause of death being metastasis, the spread of cancer to distant organs. For those patients with high-risk estrogen receptor positive (ER+) breast cancer, an increased expression of the glycoprotein MUC1 is associated with resistance to anti-hormonal therapy, metastasis and death. Tumor cells may use MUC1 to metastasize by exploiting the vascular adhesion pathways used by leukocytes during the inflammatory response. MUC1 is a type 1 transmembrane protein whose cytoplasmic tail acts as a scaffold for several signaling pathways including the non-receptor kinase Src, a signaling molecule involved in cell differentiation, proliferation, adhesion and motility. This review will highlight our current knowledge of how MUC1/ICAM-1 binding can lead to the recruitment and activation of Src and propose a novel role for lipid raft microdomains in this promigratory signaling. Improved understanding of the mechanism of metastases and the underlying signaling cascade is a prerequisite to the discovery of therapeutic targets to prevent metastasis and death in ER+ breast cancer patients.

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Abbreviations

MUC1:

Mucin 1

ICAM-1:

Intercellular adhesion molecule-1

ER+:

Estrogen receptor positive

ECD:

Extracellular domain

TMD:

Transmembrane domain

CT:

Cytoplasmic tail

CrkL:

CT10 regulator of kinase like

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Acknowledgments

We gratefully acknowledge funding from the Lilian McCullough Chair in Breast Cancer Research, the Breast Cancer Society of Canada, the Department of Defense (CDMRP), the Canadian Breast Cancer Research Alliance (NCIC) and the Canadian Breast Cancer Foundation-Prairies/NWT Region.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Laboratory of Medicine and Pathology, University of Alberta, Edmonton, AB, Canada

    Lacey Haddon

  2. Department of Laboratory of Medicine and Pathology, Room 5B4.21, Walter C. Mackenzie Health Sciences Centre, University of Alberta, 8440-112 Street, Edmonton, AB, T6G 2B7, Canada

    Judith Hugh

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  1. Lacey Haddon
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  2. Judith Hugh
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Correspondence to Judith Hugh.

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Haddon, L., Hugh, J. MUC1-mediated motility in breast cancer: a review highlighting the role of the MUC1/ICAM-1/Src signaling triad. Clin Exp Metastasis 32, 393–403 (2015). https://doi.org/10.1007/s10585-015-9711-8

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  • DOI: https://doi.org/10.1007/s10585-015-9711-8

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