scholarly journals Thrombospondin‐4 mediates hyperglycemia‐ and TGF ‐beta‐induced inflammation in breast cancer

2020 ◽  
Author(s):  
Santoshi Muppala ◽  
Roy Xiao ◽  
Jasmine Gajeton ◽  
Irene Krukovets ◽  
Dmitriy Verbovetskiy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tgf Beta ◽  
Thrombospondin 4

scholarly journals Thrombospondin-4 mediates hyperglycemia- and TGF-beta-induced inflammation in breast cancer

2020 ◽  
Author(s):  
Santoshi Muppala ◽  
Roy Xiao ◽  
Jasmine Gajeton ◽  
Irene Krukovets ◽  
Dmitriy Verbovetskiy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Growth ◽  
Breast Cancers ◽  
Tgf Beta ◽  
Matricellular Proteins ◽  
Cancer Aggressiveness ◽  
Cancer Inflammation ◽  
Tissue Specimens ◽  
Thrombospondin 4

AbstractInflammation drives the growth of tumors and is an important predictor of cancer aggressiveness. CD68, a marker of tumor-associated macrophages (TAM), is routinely used as a marker to aid in prognosis and treatment choices for breast cancer.We report that thrombospondin-4 (TSP-4) mediates breast cancer inflammation and growth in mouse models in response to hyperglycemia and TGF-beta by increasing TAM infiltration and production of inflammatory signals in tumors. Analysis of breast cancers and non-cancerous tissue specimens from hyperglycemic patients revealed that levels of TSP-4 and of macrophage marker CD68 are upregulated in diabetic tissues. TSP-4 was co-localized with macrophages in cancer tissues. Bone-marrow-derived macrophages (BMDM) responded to high glucose and TGF-beta by upregulating TSP-4 production and expression, as well as the expression of inflammatory markers.We report a novel function for TSP-4 in breast cancer: regulation of TAM infiltration and inflammation. The results of our study provide new insights into regulation of cancer growth by hyperglycemia and TGF-beta and suggest TSP-4 as a potential therapeutic target.Novelty and ImpactThrombospondin-4 (TSP-4) is a secreted extracellular protein that belongs to the family of matricellular proteins. TSP-4 is one of the top 1% of proteins upregulated in several cancers, including breast cancer. Inflammation and infiltration of macrophages drive cancer progression and metastasis and are clinically important markers of cancer aggressiveness and critical consideration in the process of selection of the appropriate therapeutic approaches. We report that TSP-4 promotes breast cancer inflammation and infiltration of macrophages and mediates the effects of hyperglycemia and TGF-beta on cancer growth and inflammation. Our work describes a role for TSP-4 in cancer inflammation and identifies the pathways, in which increased levels of TSP-4 mediate cancer growth.

Bioavailability of TGF-Beta in Breast Cancer

2005 ◽  
Author(s):  
Michael Jobling ◽  
Mary H. Barcellos-Hoff ◽  
Joni Mott
Keyword(s):  
Breast Cancer ◽  
Tgf Beta

scholarly journals Discovering novel cancer bio-markers in acquired lapatinib resistance using Bayesian methods

2021 ◽  
Author(s):  
A K M Azad ◽  
Salem A Alyami
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Sampling Methods ◽  
Differential Expression Analysis ◽  
Breast Cancer Cell Lines ◽  
Mcmc Methods ◽  
Tgf Beta ◽  
Exponential Random Graph Models ◽  
Statistical Process ◽  
Dual Inhibitor

Abstract Signalling transduction pathways (STPs) are commonly hijacked by many cancers for their growth and malignancy, but demystifying their underlying mechanisms is difficult. Here, we developed methodologies with a fully Bayesian approach in discovering novel driver bio-markers in aberrant STPs given high-throughput gene expression (GE) data. This project, namely ‘PathTurbEr’ (Pathway Perturbation Driver) uses the GE dataset derived from the lapatinib (an EGFR/HER dual inhibitor) sensitive and resistant samples from breast cancer cell lines (SKBR3). Differential expression analysis revealed 512 differentially expressed genes (DEGs) and their pathway enrichment revealed 13 highly perturbed singalling pathways in lapatinib resistance, including PI3K-AKT, Chemokine, Hippo and TGF-$\beta $ singalling pathways. Next, the aberration in TGF-$\beta $ STP was modelled as a causal Bayesian network (BN) using three MCMC sampling methods, i.e. Neighbourhood sampler (NS) and Hit-and-Run (HAR) sampler that potentially yield robust inference with lower chances of getting stuck at local optima and faster convergence compared to other state-of-art methods. Next, we examined the structural features of the optimal BN as a statistical process that generates the global structure using $p_1$-model, a special class of Exponential Random Graph Models (ERGMs), and MCMC methods for their hyper-parameter sampling. This step enabled key drivers identification that drive the aberration within the perturbed BN structure of STP, and yielded 34, 34 and 23 perturbation driver genes out of 80 constituent genes of three perturbed STP models of TGF-$\beta $ signalling inferred by NS, HAR and MH sampling methods, respectively. Functional-relevance and disease-relevance analyses suggested their significant associations with breast cancer progression/resistance.

365 Identification of a novel TGF-beta-induced signaling cascade involved in EMT and invasion of breast cancer cells

2004 ◽  
Vol 2 (8) ◽  
pp. 110
Author(s):  
A. Viloria-Petit ◽  
B. Ozdamar ◽  
R. Bose ◽  
H.-R. Wang ◽  
M. Barrios-Rodiles ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Signaling Cascade ◽  
Tgf Beta

scholarly journals Identification of Alternatively-Activated Pathways between Primary Breast Cancer and Liver Metastatic Cancer Using Microarray Data

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 753 ◽  
Author(s):  
Wang ◽  
Li ◽  
Liu ◽  
Kinnebrew ◽  
Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastasis ◽  
Calcium Signaling ◽  
Microarray Data ◽  
Primary Breast Cancer ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Tgf Beta ◽  
Breast Cancer Liver Metastasis ◽  
Alternatively Activated

Alternatively-activated pathways have been observed in biological experiments in cancer studies, but the concept had not been fully explored in computational cancer system biology. Therefore, an alternatively-activated pathway identification method was proposed and applied to primary breast cancer and breast cancer liver metastasis research using microarray data. Interestingly, the results show that cytokine-cytokine receptor interaction and calcium signaling were significantly enriched under both conditions. TGF beta signaling was found to be the hub in network topology analysis. In total, three types of alternatively-activated pathways were recognized. In the cytokine-cytokine receptor interaction pathway, four active alteration patterns in gene pairs were noticed. Thirteen cytokine-cytokine receptor pairs with inverse activity changes of both genes were verified by the literature. The second type was that some sub-pathways were active under only one condition. For the third type, nodes were significantly active in both conditions, but with different active genes. In the calcium signaling and TGF beta signaling pathways, node E2F5 and E2F4 were significantly active in primary breast cancer and metastasis, respectively. Overall, our study demonstrated the first time using microarray data to identify alternatively-activated pathways in breast cancer liver metastasis. The results showed that the proposed method was valid and effective, which could be helpful for future research for understanding the mechanism of breast cancer metastasis.

scholarly journals Screening and Bioinformatics Analysis of Competitive Endogenous RNA Regulatory Network ––Related to Circular RNA in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Tao Wang ◽  
Yi Zhang ◽  
Yan He ◽  
Yang Liu ◽  
Peng Qi
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Regulatory Network ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Tgf Beta ◽  
Qrt Pcr ◽  
Kegg Analysis ◽  
Competitive Endogenous Rna ◽  
Geo Database

Purpose. Circular RNA as a competitive endogenous RNA (ceRNA) plays a significant role in the pathogenesis and progression of breast cancer. In this study, a circular RNA-related ceRNA regulatory network was constructed, which provides new biomarkers and therapeutic targets for the treatment of breast cancer. Materials and methods. The expression profile datasets (GSE101123, GSE143564, GSE50428) of circRNAs, miRNAs, and mRNAs were downloaded from the GEO database, and then differentially expressed RNAs (DEcircRNAs, DEmiRNAs, DEmRNAs) were obtained through the CSCD, TargetScan, miRDB, and miRTarBase databases. CircRNA-miRNA pairs and miRNA-mRNA pairs were constructed. Finally, a ceRNA regulatory network was established. Downstream analysis of the ceRNA network included GO, KEGG analysis, survival analysis, sub-network construction, the BCIP, and qRT-PCR verification. Results. In total, 144 differentially expressed (DE) DEcircRNA, 221 DEmiRNA, and 1211 DEmRNA were obtained, and 96 circRNA-miRNA pairs and 139 miRNA-mRNA pairs were constructed by prediction. The ceRNA regulatory network (circRNA-miRNA-mRNA) was constructed, which included 42 circRNA, 36miRNA, and 78 mRNA. GO function annotation showed genes were mainly enriched in receptor activity activated by transforming growth factor beta (TGF-beta) and in the regulation of epithelial cell apoptosis. KEGG analysis showed genes were mainly enriched in the TGF-beta signaling, PI3K-Akt signaling, and Wnt signaling pathways. Four genes associated with survival and prognosis of breast cancer were obtained by survival analysis, the prognostic sub-network included 4 circRNA, 4 miRNA, and 4 mRNA. BCIP analysis and qRT-PCR verification confirmed that relative mRNA expression levels were consistent with those in the GEO database. Conclusion. A circRNA-related ceRNA regulatory network was constructed for breast cancer in this study and key genes affecting pathogenesis and progression were identified. These findings may help better understand and further explore the molecular mechanisms that affect the progression and pathogenesis of breast cancer.

Bioavailability of TGF-Beta in Breast Cancer

2007 ◽  
Author(s):  
Irineu Illa-Bochaca ◽  
Mary H. Barcellos-Hoff
Keyword(s):  
Breast Cancer ◽  
Tgf Beta
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