title: Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.
abstract: Breast 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.
authors.forename: Jagdeep K
authors.initials: JK
authors.lastname: Singh
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Simões
authors.forename: Sacha J
authors.initials: SJ
authors.lastname: Howell
authors.forename: Gillian
authors.initials: G
authors.lastname: Farnie
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D018719:Erb-b2 Receptor Tyrosine Kinases; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B
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