Cxcr4-ccr7 heterodimerization is a driver of breast cancer progression
Files
(Published version)
Date
2021
Authors
Poltavets, V.
Faulkner, J.W.
Dhatrak, D.
Whitfield, R.J.
McColl, S.R.
Kochetkova, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Life, 2021; 11(10):1-18
Statement of Responsibility
Valentina Poltavets, Jessica W. Faulkner, Deepak Dhatrak, Robert J. Whitfield, Shaun R. McColl and Marina Kochetkova
Conference Name
Abstract
Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to the acquisition of the pro-metastatic properties remain poorly understood. We demonstrate here that the CXCR4 and CCR7 receptor ligands, CXCL12 and CCL19, cooperatively bind and selectively elicit synergistic signalling responses in invasive breast cancer cell lines as well as primary mammary human tumour cells. Furthermore, for the first time, we have documented the presence of CXCR4-CCR7 heterodimers in advanced primary mammary mouse and human tumours where number of CXCR4-CCR7 complexes directly correlate with the severity of the disease. The functional significance of the CXCR4-CCR7 association was also demonstrated when their forced heterodimerization led to the acquisition of invasive phenotype in non-metastatic breast cancer cells. Taken together, our data establish the CXCR4-CCR7 receptor complex as a new functional unit, which is responsible for the acquisition of breast cancer cell metastatic phenotype and which may serve as a novel biomarker for invasive mammary tumours.
School/Discipline
Dissertation Note
Provenance
Description
Data source: Supplementary materials, https://www.mdpi.com/article/10.3390/life11101049/s1
Access Status
Rights
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).