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" Interleukin-8 Regulation in Triple Negative Breast Cancer Cells by Proteasome Inhibition "
Uddin, Mohammad Meenhaj
Vancurova, Ivana
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1106393
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| Doc. No
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TLpq2387962380
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| Main Entry
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Uddin, Mohammad Meenhaj
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Vancurova, Ivana
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| Title & Author
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Interleukin-8 Regulation in Triple Negative Breast Cancer Cells by Proteasome Inhibition\ Uddin, Mohammad MeenhajVancurova, Ivana
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| College
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St. John's University (New York)
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| Date
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2019
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| student score
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2019
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| Degree
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Ph.D.
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| Page No
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41
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| Abstract
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Triple negative breast cancer (TNBC) cells express increased levels of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8), which promotes their proliferation and migration. Because TNBC patients are unresponsive to current targeted therapies, new therapeutic strategies are urgently needed. While proteasome inhibition by bortezomib (BZ) or carfilzomib (CZ) has been effective in treating hematological malignancies, it has been less effective in solid tumors, including TNBC, but the mechanisms are incompletely understood. Here I report that proteasome inhibition significantly increases expression of IL-8, and its receptors CXCR1 and CXCR2, in TNBC cells. Suppression or neutralization of the BZ-induced IL-8 potentiates the BZ cytotoxic and anti-proliferative effect in TNBC cells. The IL-8 expression induced by proteasome inhibition in TNBC cells is mediated by IkB kinase (IKK), increased nuclear accumulation of p65 NFkB, and by IKK-dependent p65 recruitment to IL-8 promoter. Importantly, inhibition of IKK activity significantly decreases proliferation, migration, and invasion of BZ-treated TNBC cells. These data provide the first evidence demonstrating that proteasome inhibition increases the IL-8 signaling in TNBC cells, and suggesting that IKK inhibitors may increase effectiveness of proteasome inhibitors in treating TNBC.
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| Subject
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Biology
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Cellular biology
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Immunology
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