title: Interplay between CCR7 and Notch1 axes promotes stemness in MMTV-PyMT mammary cancer cells.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Boyle
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Krystyna A
authors.initials: KA
authors.lastname: Gieniec
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Carly E
authors.initials: CE
authors.lastname: Gregor
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Jessica W
authors.initials: JW
authors.lastname: Faulkner
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McColl
authors.affiliation: Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. marina.kochetkova@unisa.edu.au.|Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia. marina.kochetkova@unisa.edu.au.
authors.forename: Marina
authors.identifier: 0000-0002-0599-7378
authors.initials: M
authors.lastname: Kochetkova
mesh_terms: D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: C515371:Ccr7 protein, mouse; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D054400:Receptors, CCR7
keywords: Breast cancer; CCR7; Cancer stem cell; Chemokine receptor; Crosstalk; Mammary gland; Notch