Hormone receptor-independent CXCL10 production is associated with the regulation of cellular factors linked to breast cancer progression and metastasis

Ejaeidi, Ahmed; Craft, Barbara S.; Puneky, Louis V.; Lewis, Robert E.; Cruse, Julius M.

doi:10.1016/j.yexmp.2015.06.002

Cited by 43 publications

(31 citation statements)

References 66 publications

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“…Li et al reported the down-regulation of miR-34a in breast cancer [27]. Elevated CXCL10 expression in breast cancer has been validated by Ejaeidi et al [28]. Additionally, TLR4 VEGF, TGF-β1 and NF-κB have been confirmed to be activated in breast cancer [29, 30].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a Inhibition of the TLR Signaling Pathway Via CXCL10 Suppresses Breast Cancer Cell Invasion and Migration

Xu¹,

Liu²,

Yang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Breast cancer (BC) starts as a local disease, but it can metastasize to the lymph nodes and distant organs. However, the metastatic process is still poorly understood. The mRNA microarray datasets GSE26910 and GSE33447 show that CXCL10 is up-regulated in BC, and the microRNA microarray dataset GSE38167 and a network meta-analysis of microRNA expression profile studies in human BC suggest that microRNA-34a (miR-34a) is down-regulated in BC. CXCL10 was predicted as a target of miR-34a by microRNA.org. In this study, we uncovered a CXCL10-independent mechanism by which miR-34a exerts its antimetastatic activity in BC. Methods: To investigate the clinical significance of miR-34a in BC, we collected cancer tissues and paracancerous tissues from 258 patients with BC. In addition, a series of inhibitors, mimics, and siRNAs was introduced into MCF-7 and T47D cells to validate the regulatory mechanisms by which miR-34a regulates CXCL10. Next, to better understand the pivotal role of TLR signaling pathway inhibition in MCF-7 and T47D cells, we blocked the TLR signaling pathway using OxPAPC, an antagonist of TLR signaling. Results: Among BC patients, miR-34a was down-regulated, CXCL10 was up-regulated, and the TLR signaling pathway was activated. Determination of luciferase activity revealed that CXCL10 was a target of miR-34a. Through gain- and loss-of-function studies, miR-34a was demonstrated to negatively regulate CXCL10; inhibit activation of the TLR signaling pathway; significantly suppress in vitro cell proliferation, migration, and invasion; and induce apoptosis. Conclusion: Our findings suggest that functional loss or suppression of the tumor suppressor CXCL10 due to induction of miR-34a leads to inhibition of the TLR signaling pathway during breast tumorigenesis, providing a novel target for the molecular treatment of breast malignancies.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-34a Inhibition of the TLR Signaling Pathway Via CXCL10 Suppresses Breast Cancer Cell Invasion and Migration

Xu¹,

Liu²,

Yang³

et al. 2018

Cell Physiol Biochem

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“…In addition to their function as mediators of inflammatory responses, chemokines are involved in the regulation of tumor development and metastasis. Levels of the three chemokines CXCL9, CXCL10 and CXCL11 were markedly higher in metastatic BC patients as compared to healthy control sera, in the West34. Liu et al .…”

Section: Discussionmentioning

confidence: 97%

Gene expression profiling of breast cancer in Lebanese women

Makoukji

Makhoul

Khalil

et al. 2016

Sci Rep

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Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER®/Pathway Studio®. Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer.

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“…They compared tumors with complete response and partial response and identified 11 genes with differential mRNA expression. Interestingly, six of the eleven significant and marginally significant genes they identified are associated with the Wnt/B-catenin signaling pathway: BAX 29 , CCNE1 30 , PP3CA 31 , SNX1 32 , and VEGFA 33,34 , CXCL10 35 . Further work to dissect the role of this signaling pathway in controlling response to embolization is warranted, potentially by combining our mutation level analysis with Gaba et al's expression level analysis.…”

Section: Discussionmentioning

confidence: 99%

Gene Signature Associated with Upregulation of the Wnt/β-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization

Ziv

Yarmohammadi

Boas

et al. 2017

Journal of Vascular and Interventional Radiology

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Purpose To identify gene mutations in tumors undergoing trans-arterial embolization (TAE) and explore the relationship between gene mutations and tumor response to TAE. Materials and Methods This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with TAE and that had specimens analyzed for a 341-gene panel next generation sequence assay. Pathology included hepatocellular carcinoma, carcinoid, pancreatic neuroendocrine, melanoma, medullary thyroid, and liver acinar cell carcinoma. Disease, procedure data, and tumor response data were collected. Dimensionality reduction was performed using principal component analysis. A linear support vector machine was used to learn a prediction rule and identify the genes most predictive of objective tumor response (CR+PR) by mRECIST. Cross-validation was used to test the prediction on the hold-out set. Permutation testing was used to determine statistical significance of the prediction accuracy. Recursive feature elimination was used to identify the most predictive genes. Results Nine tumors were responders and eight tumors were non-responders based on mRECIST criteria at 4 months post-embolization. Using the top 2 principal components, prediction accuracy of the gene mutation signature was 70% (+/−11%), which was statistically significant (p<0.05). The most predictive genes were CTNNB1, MEN1, and NCOR1—three genes associated with the Wnt/B-catenin and hypoxia signaling pathways. Conclusions This study identifies gene mutations in tumors treated with TAE. A gene mutation signature obtained from the mutation data suggests that upregulation of the Wnt/B-catenin signaling pathway may be associated with sensitivity to TAE.

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Hormone receptor-independent CXCL10 production is associated with the regulation of cellular factors linked to breast cancer progression and metastasis

Cited by 43 publications

References 66 publications

MicroRNA-34a Inhibition of the TLR Signaling Pathway Via CXCL10 Suppresses Breast Cancer Cell Invasion and Migration

MicroRNA-34a Inhibition of the TLR Signaling Pathway Via CXCL10 Suppresses Breast Cancer Cell Invasion and Migration

Gene expression profiling of breast cancer in Lebanese women

Gene Signature Associated with Upregulation of the Wnt/β-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization

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