c-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells

Dúcka, Monika; Kučeríková, Martina; Trčka, Filip; Červinka, Jakub; Biglieri, Elisabetta; Šmarda, Jan; Borsig, Lubor; Beneš, Petr; Knopfová, Lucia

doi:10.1016/j.neo.2021.01.002

Cited by 16 publications

(13 citation statements)

References 75 publications

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“…We show that LOX mRNA is upregulated in cells on aged matrices compared to young, and when it is knocked down, E‐CAD in cells on the aged matrix is re‐localized to cell membrane. Remarkably, cytokine levels in the aged microenvironment, especially the uPA/uPAR mediators uPA, [ 59 ] uPAR, SERPINE1, [ 60 , 61 ] ANG, [ 62 ] and OPN, [ 63 , 64 ] as well as the IL1 family [ 65 , 66 ] and IL8, [ 67 ] TGF β family, [ 68 ] MMP2, [ 69 , 70 ] which largely affect cell behavior, including proliferation, migration, and differentiation, as well as cancer progression, [ 71 ] are reduced to the young matrix levels after LOX knockdown.…”

Section: Discussionmentioning

confidence: 99%

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

et al. 2021

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Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. This study shows that the aging breast ECM alone is sufficient to drive normal human mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. Decellularized breast matrix from aged mice leads to loss of E-cadherin membrane localization in KTB21 cells, increased cell motility and invasion, and increased production of inflammatory cytokines and cancer-related proteins. The aged matrix upregulates cancer-related genes in KTB21 cells and enriches a cell subpopulation highly expressing epithelial-mesenchymal transition-related genes. Lysyl oxidase knockdown reverts the aged matrix-induced changes to the young levels; it relocalizes E-cadherin to cell membrane, and reduces cell motility, invasion, and cytokine production. These results show for the first time that the aging ECM harbors key biochemical, physical, and mechanical cues contributing to invasive and cancer-like behavior in healthy and cancer mammary cells. Differential response of cells to young and aged ECMs can lead to identification of new targets for cancer treatment and prevention.

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Section: Discussionmentioning

confidence: 99%

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

et al. 2021

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“…144 different SNPs have been described in the IL-1 β gene [52]. At base pairs in these transcription sites, base transitions between C and T have been widely reported [53,54]. Recent studies have shown that IL-1β SNPs rs1143634, rs1143627, rs1143623, and rs10490571 were suggested to be associated with BC risk, while the results of the association of rs16944 with BC risk were inconsistent [55][56][57][58][59][60][61][62].…”

Section: Il-1 Single-nucleotide Polymorphisms and Breast Cancer Riskmentioning

confidence: 99%

“…It was subsequently found that c-Myb reduced autocrine signal transduction of the NF-κB pathway in BC and the ability of BC cells to migrate and cross the endothelial barrier through inhibition of the expression of IL-1α. Overexpression of IL-1α as well as the addition of recombinant protein of IL-1α activated NF-κB signaling and restored the expression of inflammatory signature genes that were suppressed by c-Myb [53]. Mouse models of BC reflect that periodontal inflammation (PI) and the resulting IL-1β promote the expression of CCL5, CXCL12, CCL2, and CXCL5, which in turn recruit MDSCs and macrophages, ultimately creating a premetastatic niche at the site of inflammation [106].…”

mentioning

confidence: 99%

Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling

Liu

Lan

et al. 2021

Mediators of Inflammation

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Breast cancer is one of the top-ranked cancers for incidence and mortality worldwide. The biggest challenges in breast cancer treatment are metastasis and drug resistance, for which work on molecular evaluation, mechanism studies, and screening of therapeutic targets is ongoing. Factors that lead to inflammatory infiltration and immune system suppression in the tumor microenvironment are potential therapeutic targets. Interleukin-1 is known as a proinflammatory and immunostimulatory cytokine, which plays important roles in inflammatory diseases. Recent studies have shown that interleukin-1 cytokines drive the formation and maintenance of an inflammatory/immunosuppressive microenvironment through complex intercellular signal crosstalk and tight intracellular signal transduction, which were found to be potentially involved in the mechanism of metastasis and drug resistance of breast cancer. Some preclinical and clinical treatments or interventions to block the interleukin-1/interleukin-1 receptor system and its up- and downstream signaling cascades have also been proven effective. This study provides an overview of IL-1-mediated signal communication in breast cancer and discusses the potential of IL-1 as a therapeutic target especially for metastatic breast cancer and combination therapy and current problems, aiming at enlightening new ideas in the study of inflammatory cytokines and immune networks in the tumor microenvironment.

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“…IL-1α is a member of IL-1 family and functions as a pro-inflammatory cytokine that promotes the expression of other cytokines, such as IL-6 [ 37 ]. M. Dúcka and colleagues showed that overexpression of IL-1α and the accumulation of its recombinant protein stimulated NF-κB signaling and restored the expression of hallmark inflammatory genes repressed by c-Myb [ 38 ]. HER2 increased drug-resistance-related CSCs in HER2+ breast cancer patients, yet the blocking of IL-1α signaling improved chemotherapy efficacy when combined with cisplatin and paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers

Tarek

El-Sayed

Woodward

et al. 2022

CIMB

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Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.

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c-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells

Cited by 16 publications

References 75 publications

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer‐Like Phenotype

Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers

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