scholarly journals BSCI-16. Olfactory receptor 5B21 drives breast cancer metastasis

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii4-iii4
Author(s):  
Mao Li ◽  
Markus Schweiger ◽  
Ichiro Nakano ◽  
Daniel Ryan ◽  
Litia Carvalho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Olfactory Receptors ◽  
Transcript Abundance ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
The Brain

Abstract Olfactory receptors (ORs), responsible for the sense of smell, play an essential role in physiological processes (even outside the nasal epithelium) and cancer. In breast cancer, however, the expression and role of ORs remain understudied. We examined the significance of ORs transcript abundance in breast cancer metastasis to different tissues including the brain, bone, and lung. While we found 20 OR genes to be differentially expressed in different metastasis versus primary tumor, OR5B21 displayed high relation with all metastases. Knockdown of OR5B21 significantly decreased the invasion and migration of breast cancer cells in culture as well as metastasis to different organs including the brain, in vivo. On the other hand, overexpression of OR5B21 in the primary cells had the opposite effect. Mechanistically, OR5B21 was associated with epithelial to mesenchymal transition through STAT3/NFkB/CEBPβ signaling pathway. We propose OR5B21 (and potentially other ORs) as a novel oncogene contributing to breast cancer metastasis, and as a potential target for therapy.

scholarly journals GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Wenqian Yu ◽  
Wei Huang ◽  
Yang Yang ◽  
Rongfang Qiu ◽  
Yi Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Gata3 Expression ◽  
Histone H3k27

Abstract GATA3 has emerged as a prominent transcription factor required for maintaining mammary-gland homeostasis. GATA3 loss is associated with aggressive breast cancer development, but the mechanism by which breast cancer is affected by the loss of GATA3 function remains unclear. Here, we report that GATA3 expression is positively correlated with the expression of UTX, a histone H3K27 demethylase contained in the MLL4 methyltransferase complex, and that GATA3 recruits the chromatin-remodeling MLL4 complex and interacts directly with UTX, ASH2L, and RBBP5. Using RNA sequencing and chromatin immunoprecipitation and sequencing, we demonstrate that the GATA3/UTX complex synergistically regulates a cohort of genes including Dicer and UTX, which are critically involved in the epithelial-to-mesenchymal transition (EMT). Our results further show that the GATA3-UTX-Dicer axis inhibits EMT, invasion, and metastasis of breast cancer cells in vitro and the dissemination of breast cancer in vivo. Our study implicates the GATA3-UTX-Dicer axis in breast cancer metastasis and provides new mechanistic insights into the pathophysiological function of GATA3.

Role of E2F3 and shugoshin I in epithelial-to-mesenchymal transition and cell invasion in breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13100-e13100
Author(s):  
Shirley Jusino ◽  
Srikumar P. Chellappan ◽  
Harold I. Saavedra
Keyword(s):  
Breast Cancer ◽  
Cell Invasion ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Cellular Proliferation ◽  
Protein Localization ◽  
Breast Cancer Metastasis ◽  
Mrna Levels ◽  
Mesenchymal Transition

e13100 Background: Triple-negative breast cancer (TNBC) is the most aggressive and poorly prognostic breast cancer subtype, yet there are currently no biological therapies against this subtype. Our laboratory is finding the sources of novel biological targets in TNBC by studying the E2F transcription factors, which are essential for cellular proliferation and maintenance of genomic stability. While the deregulated Rb/E2F pathway signals the epithelial-to-mesenchymal transition (EMT), the underlining mechanism of how E2Fs drive EMT in TNBC remains unknown. We recently published that the E2F transcriptional activators (E2Fs) are overexpressed in the vast majority of TNBC and that their overexpression upregulates mitotic kinases such as TTK, which we have shown to induce EMT and invasion in TNBC cells. We also demonstrated that the E2Fs maintain genomic integrity in part through Shugoshin I (SGO1), which normally controls chromosome cohesion; however, the role of SGO1 in EMT in breast cancer is unknown. Our hypothesis is that E2F3 and SGO1 are highly expressed in TNBC and that their overexpression modulates EMT genes, thus promoting cell invasion. Methods: To test our hypothesis, we conducted siRNA transfection to knockdown E2F3 and SGO1 in MDA-MB-231 and Hs578t, which are TNBC cells. After 48 hours, we evaluated mRNA levels of EMT-related genes after E2F3 or SGO1 depletion using RT-PCR analysis. We also evaluated the effects of SGO1 depletion in protein localization by immunofluorescence. Furthermore, we evaluated the invasive behavior of MDA-MB-231 and Hs578t cells after SGO1 depletion using a Boyden Chamber Assay. Results: Our results demonstrate that E2F3 and SGO1 depletion decrease MMP3 mRNA levels. Moreover, E2F3 and SGO1 depletion restore E-cadherin expression and localization. Furthermore, E2F3 and SGO1 depletion significantly reduce cell invasion in MDA-MB-231 and Hs578t cells. Conclusions: Our results suggest that SGO1 is a promising drug target for breast cancer metastasis since EMT and invasion are essential early steps in breast cancer metastasis and E2F3 is presently undruggable.

Targeting Monoacylglycerol Lipase in Triple Negative Breast Cancer Reduced Tumor-Associated Inflammation, Tumor Growth and Tumor Colonization in the Brain

2021 ◽  
Author(s):  
Othman Benchama ◽  
Sergiy Tyukhtenko ◽  
Michael S. Malamas ◽  
Mark K. Williams ◽  
Alexandros Makriyannis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Monoacylglycerol Lipase ◽  
Breast Cancers ◽  
Novel Treatments ◽  
The Brain

Abstract While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using the selective MAGL inhibitor AM9928 (hMAGL IC50 = 9nM, with prolonged pharmacodynamic effects of 46 hours residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Knockdown of MAGL by siRNA or treatment with AM9928 increased the expression of the adherent junction E-cadherin, known to be regulated by MAGL. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.

scholarly journals Long Non-Coding RNA: Dual Effects on Breast Cancer Metastasis and Clinical Applications

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1802 ◽  
Author(s):  
Qi-Yuan Huang ◽  
Guo-Feng Liu ◽  
Xian-Ling Qian ◽  
Li-Bo Tang ◽  
Qing-Yun Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Regulatory Effects ◽  
Long Non Coding Rna

As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain

2006 ◽  
Vol 56 (5) ◽  
pp. 1001-1010 ◽  
Author(s):  
Chris Heyn ◽  
John A. Ronald ◽  
Soha S. Ramadan ◽  
Jonatan A. Snir ◽  
Andrea M. Barry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Single Cell ◽  
Cell Fate ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Single Cell Level ◽  
Cell Level ◽  
The Brain

scholarly journals Exosomal microRNAs: Pleiotropic Impacts on Breast Cancer Metastasis and Their Clinical Perspectives

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 307
Author(s):  
Li-Bo Tang ◽  
Shu-Xin Ma ◽  
Zhuo-Hui Chen ◽  
Qi-Yuan Huang ◽  
Long-Yuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Sensitivity ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition ◽  
Diagnosis And Prognosis ◽  
Pathological Conditions ◽  
Mesenchymal To Epithelial Transition ◽  
Exosomal Mirnas

As a major threat factor for female health, breast cancer (BC) has garnered a lot of attention for its malignancy and diverse molecules participating in its carcinogenesis process. Among these complex carcinogenesis processes, cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis are the major causes for the occurrence of metastasis and chemoresistance which account for cancer malignancy. MicroRNAs packaged and secreted in exosomes are termed “exosomal microRNAs (miRNAs)”. Nowadays, more researches have uncovered the roles of exosomal miRNAs played in BC metastasis. In this review, we recapitulated the dual actions of exosomal miRNAs exerted in the aggressiveness of BC by influencing migration, invasion, and distant metastasis. Next, we presented how exosomal miRNAs modify angiogenesis and stemness maintenance. Clinically, several exosomal miRNAs can govern the transformation between drug sensitivity and chemoresistance. Since the balance of the number and type of exosomal miRNAs is disturbed in pathological conditions, they are able to serve as instructive biomarkers for BC diagnosis and prognosis. More efforts are needed to connect the theoretical studies and clinical traits together. This review provides an outline of the pleiotropic impacts of exosomal miRNAs on BC metastasis and their clinical implications, paving the way for future personalized drugs.

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