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Molecular Cancer
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Short communication

Interplay between CCR7 and Notch1 axes promotes stemness in MMTV-PyMT mammary cancer cells

Authors: Sarah T. Boyle, Krystyna A. Gieniec, Carly E. Gregor, Jessica W. Faulkner, Shaun R. McColl, Marina Kochetkova

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Background

Breast cancer is the major cause of cancer-related mortality in women. It is thought that quiescent stem-like cells within solid tumors are responsible for cancer maintenance, progression and eventual metastasis. We recently reported that the chemokine receptor CCR7, a multi-functional regulator of breast cancer, maintains the stem-like cell population.

Methods

This study used a combination of molecular and cellular assays on primary mammary tumor cells from the MMTV-PyMT transgenic mouse with or without CCR7 to examine the signaling crosstalk between CCR7 and Notch pathways.

Results

We show for the first time that CCR7 functionally intersects with the Notch signaling pathway to regulate mammary cancer stem-like cells. In this cell subpopulation, CCR7 stimulation activated the Notch signaling pathway, and deletion of CCR7 significantly reduced the levels of activated cleaved Notch1. Moreover, blocking Notch activity prevented specific ligand-induced signaling of CCR7 and augmentation of mammary cancer stem-like cell function.

Conclusion

Crosstalk between CCR7 and Notch1 promotes stemness in mammary cancer cells and may ultimately potentiate mammary tumor progression. Therefore, dual targeting of both the CCR7 receptor and Notch1 signaling axes may be a potential therapeutic avenue to specifically inhibit the functions of breast cancer stem cells.
Appendix
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Metadata
Title
Interplay between CCR7 and Notch1 axes promotes stemness in MMTV-PyMT mammary cancer cells
Authors
Sarah T. Boyle
Krystyna A. Gieniec
Carly E. Gregor
Jessica W. Faulkner
Shaun R. McColl
Marina Kochetkova
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0592-0

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