scholarly journals STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 429
Author(s):  
Sarah Q. To ◽  
Rhynelle S. Dmello ◽  
Anna K. Richards ◽  
Matthias Ernst ◽  
Ashwini L. Chand
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activity ◽  
Therapeutic Potential ◽  
Metastatic Potential ◽  
Hallmarks Of Cancer ◽  
Cellular Processes ◽  
Stat3 Signaling ◽  
Gp130 Receptor ◽  
Heterogeneous Nature ◽  
Specific Receptors

Interleukin (IL)-6 family cytokines, such as IL-6 and IL-11, are defined by the shared use of the gp130 receptor for the downstream activation of STAT3 signaling and the activation of genes which contribute to the “hallmarks of cancer”, including proliferation, survival, invasion and metastasis. Increased expression of these cytokines, or the ligand-specific receptors IL-6R and IL-11RA, in breast tumors positively correlate to disease progression and poorer patient outcome. In this review, we examine evidence from pre-clinical studies that correlate enhanced IL-6 and IL-11 mediated gp130/STAT3 signaling to the progression of breast cancer. Key processes by which the IL-6 family cytokines contribute to the heterogeneous nature of breast cancer, immune evasion and metastatic potential, are discussed. We examine the latest research into the therapeutic targeting of IL-6 family cytokines that inhibit STAT3 transcriptional activity as a potential breast cancer treatment, including current clinical trials. The importance of the IL-6 family of cytokines in cellular processes that promote the development and progression of breast cancer warrants further understanding of the molecular basis for its actions to help guide the development of future therapeutic targets.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

scholarly journals In silico Analysis of Combinatorial microRNA Activity Reveals Target Genes and Pathways Associated with Breast Cancer Metastasis

2011 ◽  
Vol 10 ◽  
pp. CIN.S6631 ◽  
Author(s):  
Alan A. Dombkowski ◽  
Zakia Sultana ◽  
Douglas B. Craig ◽  
Hasan Jamil
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Target Genes ◽  
In Silico Analysis ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Computational Method ◽  
Cytoskeleton Organization ◽  
Cellular Processes ◽  
Therapeutic Development

Aberrant microRNA activity has been reported in many diseases, and studies often find numerous microRNAs concurrently dysregulated. Most target genes have binding sites for multiple microRNAs, and mounting evidence indicates that it is important to consider their combinatorial effect on target gene repression. A recent study associated the coincident loss of expression of six microRNAs with metastatic potential in breast cancer. Here, we used a new computational method, miR-AT!, to investigate combinatorial activity among this group of microRNAs. We found that the set of transcripts having multiple target sites for these microRNAs was significantly enriched with genes involved in cellular processes commonly perturbed in metastatic tumors: cell cycle regulation, cytoskeleton organization, and cell adhesion. Network analysis revealed numerous target genes upstream of cyclin D1 and c-Myc, indicating that the collective loss of the six microRNAs may have a focal effect on these two key regulatory nodes. A number of genes previously implicated in cancer metastasis are among the predicted combinatorial targets, including TGFB1, ARPC3, and RANKL. In summary, our analysis reveals extensive combinatorial interactions that have notable implications for their potential role in breast cancer metastasis and in therapeutic development.

scholarly journals Cancer-associated Fibroblasts Release Exosomal CBFB That Dictate an Aggressive Bone Metastasis Phenotype in Breast Cancer 

2020 ◽  
Author(s):  
Chih Ming Su ◽  
Wen-Chien Huang ◽  
Kuang-Tai Kuo ◽  
Ming-Shou Hsieh ◽  
Iat-Hang Fong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Standard Procedure ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Breast Cancer Cell Lines

Abstract Background: Breast cancer up to date remains the one of the most prevalent female malignancies in the world. Better prognostic and therapeutic biomarkers are urgently required for these patients. Circulating exosomes are shown to participate in tumorigenesis including distance metastasis and of prognostic/therapeutic potential. Methods: Sera from control health, primary breast cancer, and bone metastatic breast cancer patients were collected. The Exosome were isolated from collected sera and culture medium from previously steps, and a standard procedure was performed. We utilized MDA-MB-436-derived xenograft mouse model to demonstrate that silencing CBFB (core binding factor subunit β) significantly reduced bone-metastasis in association with reduced expression of OPN, IL-6, Runx2 and OPN as well as reduced exosomes containing CBFB.Results: We found that circulating exosomes (Exos), from bone metastatic patients with breast cancer, were enriched with CBFB. Fibroblasts co-cultured with Exos showed increased α-SMA, vimentin expression and increased secretion of IL-6 and OPN; non-metastatic breast cancer cells co-cultured with Exos exhibited increased markers including vimentin, snail1, CXCR4 and Runx2. Subsequent analysis revealed that these Exos were enriched with bone metastasis associated maker CBFB. Gene-silencing experiments metastatic MDA-MB-436 and MDA-MB-157 cells, demonstrated that CBFB significantly reduced metastatic potential, reflected by the suppression of vimentin, CXCR4, snail1 and Runx2, CD44 and OPN. In contrary, CBFB-overexpression resulted in the increased metastasis associated genes in non-metastatic T47D and MCF7 cells. The CBFB-enriched exosomes derived from MDA-MB-436 enhanced metastatic phenotypes of low metastatic potential breast cancer cell lines. Conclusion: We demonstrated the essential roles of CBFB in the promotion of bone metastasis in breast cancer cells. The suppression of CBFB led to the decreased tumor burden and bone metastasis in association with decreased markers of bone metastasis including CXCR4, Snail, CD44, OPN, Runx2 and IL-6.

scholarly journals Cancer-Associated Fibroblasts Release Exosomal CBFB That Dictate an Aggressive Bone Metastasis Phenotype in Breast Cancer

2020 ◽  
Author(s):  
Chih-Ming Su ◽  
Yu-Hsin Lai ◽  
Oluwaseun Adebayo Bamodu ◽  
Kuang-Tai Kuo ◽  
Iat-Hang Fong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Standard Procedure ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Breast Cancer Cell Lines

Abstract BackgroundBreast cancer up to date remains the one of the most prevalent female malignancies in the world. Better prognostic and therapeutic biomarkers are urgently required for these patients. Circulating exosomes are shown to participate in tumorigenesis including distance metastasis and of prognostic/therapeutic potential. MethodsSera from control health, primary breast cancer, and bone metastatic breast cancer patients were collected. The Exosome were isolated from collected sera and culture medium from previously steps, and a standard procedure was performed. We utilized MDA-MB-436-derived xenograft mouse model to demonstrate that silencing CBFB (core binding factor subunit β) significantly reduced bone-metastasis in association with reduced expression of OPN, IL-6, Runx2 and OPN as well as reduced exosomes containing CBFB.ResultsWe found that circulating exosomes (Exos), from bone metastatic patients with breast cancer, were enriched with CBFB. Fibroblasts co-cultured with Exos showed increased α-SMA, vimentin expression and increased secretion of IL-6 and OPN; non-metastatic breast cancer cells co-cultured with Exos exhibited increased markers including vimentin, snail1, CXCR4 and Runx2. Subsequent analysis revealed that these Exos were enriched with bone metastasis associated maker CBFB. Gene-silencing experiments metastatic MDA-MB-436 and MDA-MB-157 cells, demonstrated that CBFB significantly reduced metastatic potential, reflected by the suppression of vimentin, CXCR4, snail1 and Runx2, CD44 and OPN. In contrary, CBFB-overexpression resulted in the increased metastasis associated genes in non-metastatic T47D and MCF7 cells. The CBFB-enriched exosomes derived from MDA-MB-436 enhanced metastatic phenotypes of low metastatic potential breast cancer cell lines. ConclusionWe demonstrated the essential roles of CBFB in the promotion of bone metastasis in breast cancer cells. The suppression of CBFB led to the decreased tumor burden and bone metastasis in association with decreased markers of bone metastasis including CXCR4, Snail, CD44, OPN, Runx2 and IL-6.

Biological Role of CDK 11 and 12 in Cell Cycle and its Function in Tumorigenesis

2020 ◽  
Author(s):  
Shamim Mushtaq
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Web Of Science ◽  
The Body ◽  
Main Role ◽  
Hallmarks Of Cancer ◽  
Cyclin Dependent Kinases ◽  
Tumor Studies ◽  
Cycle Regulation

Uninhibited proliferation and abnormal cell cycle regulation are the hallmarks of cancer. The main role of cyclin dependent kinases is to regulate the cell cycle and cell proliferation. These protein kinases are frequently down regulated or up regulated in various cancers. Two CDK family members, CDK 11 and 12, have contradicting views about their roles in different cancers. For example, one study suggests that the CDK 11 isoforms, p58, inhibits growth of breast cancer whereas, the CDK 11 isoform, p110, is highly expressed in breast tumor. Studies regarding CDK 12 show variation of opinion towards different parts of the body, however there is a consensus that upregulation of cdk12 increases the risk of breast cancer. Hence, CDK 11 and CDK 12 need to be analyzed to confirm their mechanism and their role regarding therapeutics, prognostic value, and ethnicity in cancer. This article gives an outline on both CDKs of information known up to date from Medline, PubMed, Google Scholar and Web of Science search engines, which were explored and thirty relevant researches were finalized.

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