title: Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.
abstract: Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.
authors: Department of Clinical Cancer Prevention and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Zachary C
authors: ZC
authors: Hartman
authors: Graham M
authors: GM
authors: Poage
authors: Petra
authors: P
authors: den Hollander
authors: Anna
authors: A
authors: Tsimelzon
authors: Jamal
authors: J
authors: Hill
authors: Nattapon
authors: N
authors: Panupinthu
authors: Yun
authors: Y
authors: Zhang
authors: Abhijit
authors: A
authors: Mazumdar
authors: Susan G
authors: SG
authors: Hilsenbeck
authors: Gordon B
authors: GB
authors: Mills
authors: Powel H
authors: PH
authors: Brown
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines; D005260:Female; D064593:Heterografts; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D016016:Proportional Hazards Models; D015398:Signal Transduction; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D000093242:Interleukin-6 Inhibitors
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