Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.
AffiliationBreast Biology, Institute of Cancer Sciences, University of Manchester, Paterson Building, Wilmslow Road, Manchester, M20 4BX, UK. firstname.lastname@example.org.
MetadataShow full item record
AbstractBreast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival.
CitationRecent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells. 2013, 15 (4):210 Breast Cancer Res.
JournalBreast Cancer Research
- Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms.
- Authors: Singh JK, Farnie G, Bundred NJ, Simões BM, Shergill A, Landberg G, Howell SJ, Clarke RB
- Issue date: 2013 Feb 1
- Breast cancer stem cells: we've got them surrounded.
- Authors: Korkaya H, Wicha MS
- Issue date: 2013 Feb 1
- An autocrine inflammatory forward-feedback loop after chemotherapy withdrawal facilitates the repopulation of drug-resistant breast cancer cells.
- Authors: Jia D, Li L, Andrew S, Allan D, Li X, Lee J, Ji G, Yao Z, Gadde S, Figeys D, Wang L
- Issue date: 2017 Jul 13
- Targeting IL-8 signalling to inhibit breast cancer stem cell activity.
- Authors: Singh JK, Simões BM, Clarke RB, Bundred NJ
- Issue date: 2013 Nov
- Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases.
- Authors: Ha H, Debnath B, Neamati N
- Issue date: 2017