1. Interleukin-1 and Nuclear Factor Kappa B Signaling Promote Breast Cancer Progression and Treatment Resistance.
- Author
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Diep S, Maddukuri M, Yamauchi S, Geshow G, and Delk NA
- Subjects
- Cytokines metabolism, Female, Humans, Transcription Factor AP-1 metabolism, Tumor Necrosis Factor-alpha metabolism, Breast Neoplasms drug therapy, Interleukin-1 metabolism, NF-kappa B metabolism
- Abstract
While meant for wound healing and immunity in response to injury and infection, inflammatory signaling is usurped by cancerous tumors to promote disease progression, including treatment resistance. The interleukin-1 (IL-1) inflammatory cytokine family functions in wound healing and innate and adaptive immunity. Two major, closely related IL-1 family members, IL-1α and IL-1β, promote tumorigenic phenotypes and contribute to treatment resistance in cancer. IL-1 signaling converges on transactivation of the Nuclear Factor Kappa B (NF-κB) and Activator protein 1 (AP-1) transcription factors. NF-κB and AP-1 signaling are also activated by the inflammatory cytokine Tumor Necrosis Factor Alpha (TNFα) and microbe-sensing Toll-Like Receptors (TLRs). As reviewed elsewhere, IL-1, TNFα, and TLR can promote cancer progression through NF-κB or AP-1. In this review, we focus on what is known about the role of IL-1α and IL-1β in breast cancer (BCa) progression and therapeutic resistance, and state evidence for the role of NF-κB in mediating IL-1-induced BCa progression and therapeutic resistance. We will present evidence that IL-1 promotes BCa cell proliferation, BCa stem cell expansion, angiogenesis, and metastasis. IL-1 also regulates intracellular signaling and BCa cell hormone receptor expression in a manner that confers a growth advantage to the tumor cells and allows BCa cells to evade therapy. As such, the IL-1 receptor antagonist, anakinra, is in clinical trials to treat BCa and multiple other cancer types. This article presents a review of the literature from the 1990s to the present, outlining the evidence supporting a role for IL-1 and IL-1-NF-κB signaling in BCa progression.
- Published
- 2022
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