IKKε regulates the breast cancer stem cell phenotype

Orlova, Zhanna; Pruefer, Franz; Castro-Oropeza, Rosario; Ordaz-Ramos, Alejandro; Zampedri, Cecilia; Maldonado, Vilma; Vázquez-Santillán, Karla; Meléndez-Zajgla, Jorge

doi:10.1016/j.bbamcr.2019.01.002

Cited by 15 publications

(11 citation statements)

References 60 publications

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“…The lowest levels of expression were found in the MDA-MB-361 and HS578T and MDA231 cell lines, which have a high invasive capacity, whereas the highest levels were found in the MDA-MB-453, T47D and MCF-7 cell lines, which have lower invasive capacity ( Figure 1C). stem-like phenotype after IKKε was overexpressed (21). It is well known that three-dimensional (3D) MCF-7 culture (spheroids) mimic the main features of human solid tumors including migration, invasion, proliferation, stemness features, and an increase of IKKε level (21).…”

Section: Resultsmentioning

confidence: 99%

“…stem-like phenotype after IKKε was overexpressed (21). It is well known that three-dimensional (3D) MCF-7 culture (spheroids) mimic the main features of human solid tumors including migration, invasion, proliferation, stemness features, and an increase of IKKε level (21). We evaluated the expression of lincRNA-RP11400k9.4 in 3D cultures.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, long intergenic non-coding RNA (lincRNA) RP11400k9.4 was pointed out as a possible marker for triple-negative breast cancer (18)(19)(20). In addition, we found that this lincRNA is associated with deregulation of inhibitor of nuclear factor kappa B kinase subunit epsilon (IKKε) kinase and the stem cell phenotype in breast cancer (21). In this study, we aimed to elucidate the role of this lincRNA in breast cancer cells.…”

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confidence: 99%

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lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells

Fernández-Rojas

Meléndez-Zajgla

Lagunas

2020

Cancer Genomics Proteomics

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Background/Aim: Several works in the past decades pointed out the key role of long intergenic non-coding RNA (lincRNA) in breast cancer development. Here in we report for first time the importance of deregulation of lincRNA RP11-400K9.4 in breast cancer cells which played a role in cell survival and migration. Materials and Methods: After RP11-400K9.4 silencing by short hairpin RNAs or overexpression by GeneBlocks, real-time quantitative polymerase chain reaction (RT-PCR), microarray, migration, proliferation and viability assay were performed. Results: RP11-400K9.4 expression was mainly in the cytoplasmic fraction in 2D culture. Overexpression of RP11-400K9.4 led to a reduction of migration by MCF-7 and MDA-MB-368 cells and an increase in cellular survival after UV-C radiation. Bioinformatic analyses highlighted irradiationinduced DNA damage, DNA repair and cell-cycle pathways as the mainly affected by RP11-400K9.4. Furthermore RT-PCR assay demonstrated the overexpression of baculoviral IAP repeat containing 3 (BIRC3) a known oncogene that promotes radiotherapy resistance through the nuclear factor kappa B (NFĸB) pathway. Conclusion: RP11-400K9.4 participates in the modulation of migration and survival processes probably via the BIRC3/NFĸB pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells

Fernández-Rojas

Meléndez-Zajgla

Lagunas

2020

Cancer Genomics Proteomics

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“…For example, by integrative genomic approaches, Boehm et al found breast cancer cells harbor IKBKE amplifications, which is associated with tumorigenesis [39]. Several recent studies also showed that IKBKE induces tumorigenesis and cancer stem cell phenotype in TNBC [40,41]. In addition, IKBKE has been reported to promote cell proliferation and attenuate cell senescence in HER2 positive breast cancer [42].…”

Section: Discussionmentioning

confidence: 99%

IKBKE is a critical mediator of TAM-induced breast cancer resistance to BET inhibition

Qiao¹,

Chen²,

Mi³

et al. 2020

Preprint

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Background: BET inhibitors (BETi) exhibit a strong anti-tumor activity in triple-negative breast cancer (TNBC). However, BETi resistance has been reported in TNBC. The mechanisms of resistance have not been demonstrated. Tumor-associated macrophages (TAMs) are frequently involved in cancer cells resistance to chemotherapy, also associated with poor prognosis in TNBC. However, the role of TAMs in BETi resistance remains unknown. Method: The expression of RNA was evaluated by qRT-PCR. Protein was detected by Western blot, immunofluorescence and Enzyme linked immunosorbent assay (ELISA). Cell viability was detected by Cell Counting Kit-8 (CCK-8). Apoptosis was evaluated by Annexin V-FITC/PI, TUNEL assays and Hoechst 33258 staining. NF-κB activities were detected by luciferase reporter assays. Mice model of breast cancer was established with subcutaneous xenograft tumor. Detailed mechanistic studies were performed by using inhibitors, RNA interference and DNA transfections. Results: Here, we found that BETi JQ1 and I-BET151 exerted anti-tumor effects in TNBC by decreasing IKBKE expression to attenuate NF-κB signaling. BET inhibition was found to downregulate IKBKE levels through BRD2/E2F1 axis. Moreover, we firstly found that TNBC-stimulated TAMs activated NF-κB signaling by upregulating IKBKE expression to enhance breast cancer cells resistance to BETi. The IKBKE levels were also proved to be higher in clinical TNBC tissues than Non-TNBC tissues, suggesting feedback induction of IKBKE expression by TNBC-stimulated TAMs in TNBC. In addition, the induction of IKBKE by TAMs in TNBC cells was identified to be associated with STAT3 signaling, which was activated by TAM-secreted IL-6 and IL-10. Lastly, the combination of inhibitors of BET and STAT3 exerted a synergistic inhibition effects in TAM-cocultured or TAM CM-treated TNBC cells in vitro and in vivo . Conclusion: Altogether, our findings illustrated TNBC-activated macrophages conferred TNBC cells resistance to BETi via IL-6 or IL-10/STAT3/IKBKE/NF-κB axis. Blockade of IKBKE or double inhibition of BET and STAT3 might be a novel strategy for treatment of TNBC.

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“…Em estudos in vivo, mostrados na tabela 1, a Curcumina regulou negativamente as citocinas inflamatórias que causam caquexia no CM (30,44).…”

Section: Curcuminaunclassified

Prevenção e Tratamento da Caquexia no Câncer de Mama por Probiótico e Curcumina

Zilli¹,

Simas²

2019

Braz. J. Nat. Sci

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O objetivo desse artigo é realizar uma revisão sistêmica sobre o tratamento e a prevenção da caquexia no câncer de mama (CM) com o uso de probióticos e curcumina, o processo no qual ocorre degradação proteica, lipólise excessiva e inflamação crônica através de estímulos de HIF-1/IL-6/TGF-β/TNF/NF-kB, desencadeando angiogênese, invasão e metástase tumoral, levando a um pior prognóstico do câncer de mama. Para atingir o objetivo foi realizada uma revisão sobre os mecanismos bioquímicos pelos quais a caquexia atinge os pacientes com CM e a inibição desses através da utilização de probióticos e curcumina. Os probióticos inibem as vias STAT/NF-kB/COX-2 e estimulam PPARγ, inibindo a inflamação crônica e a lipólise excessiva. A curcumina é eficiente na captação de espécies reativas ao oxigênio (ERO) e na inibição do fator induzível por hipóxia 1 (HIF-1), consequentemente inibindo o estresse oxidativo total do organismo, melhorando a sensibilidade a radioterapia de células neoplásicas e causando diminuição do metabolismo tumoral. De acordo com os artigos estudados, os probióticos e a curcumina são duas estratégias eficientes na prevenção e tratamento da caquexia no CM, melhorando o prognóstico da doença. Os estudos analisados descrevem que, tanto os probióticos como a curcumina são seguros, para administração em pacientes com câncer durante tratamento radioterápico e quimioterápico.

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IKKε regulates the breast cancer stem cell phenotype

Cited by 15 publications

References 60 publications

lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells

lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells

IKBKE is a critical mediator of TAM-induced breast cancer resistance to BET inhibition

Prevenção e Tratamento da Caquexia no Câncer de Mama por Probiótico e Curcumina

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