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

Molecular Cancer

Short Communication

Sarah T. Boyle¹  Marina Kochetkova¹  Carly E. Gregor²  Krystyna A. Gieniec²  Jessica W. Faulkner²  Shaun R. McColl² 

[1] Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia;Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia;Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia;

关键词: Breast cancer;    Mammary gland;    Chemokine receptor;    CCR7;    Notch;    Cancer stem cell;    Crosstalk;   

DOI  :  10.1186/s12943-017-0592-0

 received in 2016-10-17, accepted in 2017-01-18,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBreast 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.MethodsThis 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.ResultsWe 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.ConclusionCrosstalk 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.

【 授权许可】

CC BY   
© The Author(s). 2017