scholarly journals A Novel Role for Brain and Acute Leukemia Cytoplasmic (BAALC) in Human Breast Cancer Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Madeleine Birgersson ◽  
Mengna Chi ◽  
Chrissy Miller ◽  
Joshua S. Brzozowski ◽  
Jeffrey Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Normal Breast ◽  
Migration And Invasion ◽  
Free Survival ◽  
Invasion And Migration ◽  
And Migration ◽  
Disease Free

Brain and Acute Leukemia, Cytoplasmic (BAALC) is a protein that controls leukemia cell proliferation, differentiation, and survival and is overexpressed in several cancer types. The gene is located in the chromosomal region 8q22.3, an area commonly amplified in breast cancer and associated with poor prognosis. However, the expression and potential role of BAALC in breast cancer has not widely been examined. This study investigates BAALC expression in human breast cancers with the aim of determining if it plays a role in the pathogenesis of the disease. BAALC protein expression was examined by immunohistochemistry in breast cancer, and matched lymph node and normal breast tissue samples. The effect of gene expression on overall survival (OS), disease-free and distant metastasis free survival (DMFS) was assessed in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis.

scholarly journals Long noncoding RNA FGF14-AS2 inhibits breast cancer metastasis by regulating the miR-370-3p/FGF14 axis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yucui Jin ◽  
Ming Zhang ◽  
Rui Duan ◽  
Jiashu Yang ◽  
Ying Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Clinical Stage ◽  
Breast Cancer Metastasis ◽  
Normal Breast ◽  
Advanced Clinical Stage ◽  
Cancer Tissues

Abstract Long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, including breast cancer. However, the overall biological roles and clinical significance of most lncRNAs are not fully understood. This study aimed to elucidate the potential role of a novel lncRNA FGF14-AS2 and the mechanisms underlying metastasis in breast cancer. The lncRNA FGF14-AS2 was significantly downregulated in breast cancer tissues; patients with lower FGF14-AS2 expression had advanced clinical stage. In vitro and in vivo assays of FGF14-AS2 alterations revealed a complex integrated phenotype affecting breast cancer cell migration, invasion, and tumor metastasis. Mechanistically, FGF14-AS2 functioned as a competing endogenous RNA of miR-370-3p, thereby leading to the activation of its coding counterpart, FGF14. Clinically, we observed increased miR-370-3p expression in breast cancer tissues, whereas FGF14 expression was decreased in breast cancer tissues compared to the adjacent normal breast tissues. FGF14-AS2 expression was significantly negatively correlated with miR-370-3p expression, and correlated positively to FGF14 expression. Collectively, our findings support a model in which the FGF14-AS2/miR-370-3p/FGF14 axis is a critical regulator in breast cancer metastasis, suggesting a new therapeutic direction in breast cancer.

scholarly journals Expression of Cadherin-17 Promotes Metastasis in a Highly Bone Marrow Metastatic Murine Breast Cancer Model

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Tomoko Okada ◽  
Atsushi Kurabayashi ◽  
Nobuyoshi Akimitsu ◽  
Mutsuo Furihata
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Subcutaneous Injection ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Gene And Protein Expression ◽  
Mouse Breast Cancer ◽  
And Migration

We previously established 4T1E/M3 highly bone marrow metastatic mouse breast cancer cells through in vivo selection of 4T1 cells. But while the incidence of bone marrow metastasis of 4T1E/M3 cells was high (~80%) when injected intravenously to mice, it was rather low (~20%) when injected subcutaneously. Therefore, using 4T1E/M3 cells, we carried out further in vitro and in vivo selection steps to establish FP10SC2 cells, which show a very high incidence of metastasis to lungs (100%) and spines (85%) after subcutaneous injection into mice. qRT-PCR and western bolt analysis revealed that cadherin-17 gene and protein expression were higher in FP10SC2 cells than in parental 4T1E/M3 cells. In addition, immunostaining revealed the presence of cadherin-17 at sites of bone marrow and lung metastasis after subcutaneous injection of FP10SC2 cells into mice. Suppressing cadherin-17 expression in FP10SC2 cells using RNAi dramatically decreased the cells’ anchorage-independent growth and migration in vitro and their metastasis to lung and bone marrow in vivo. These findings suggest that cadherin-17 plays a crucial role in mediating breast cancer metastasis to bone marrow.

scholarly journals A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xue Kong ◽  
Juan Li ◽  
Yanru Li ◽  
Weili Duan ◽  
Qiuchen Qi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Breast Cancer Patients

AbstractBreast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.

scholarly journals Long Noncoding RNA HCG11 Acts as a Tumor Suppressor in Gastric Cancer by Regulating miR-942-5p/BRMS1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Qingmei Zhang ◽  
Keli Yang ◽  
Jie Li ◽  
Fang Chen ◽  
Yan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Metastasis Suppressor ◽  
Invasion And Migration ◽  
And Migration

The functions of long noncoding RNAs (lncRNAs) have been widely investigated in human cancers, including gastric cancer (GC). The purpose of this study was to elucidate the role of lncRNA HCG11 in GC. In this study, mRNA and protein expressions were detected by quantitative real-time polymerase chain reaction assays (RT-qPCR) and Western blot analysis. The proliferation ability of GC cells was examined by (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide) MTT assays. The invasion and migration abilities of GC cells were evaluated by Transwell assays. The binding sites between miR-942-5p and HCG11/BRMS1 were confirmed by dual-luciferase reporter assays. Results showed that LncRNA HCG11 was downregulated in GC cells. Functionally, overexpression of HCG11 inhibited GC cell proliferation, migration, and invasion. In addition, lncRNA HCG11 was found to act as a molecular sponge of miR-942-5p. Furthermore, miR-942-5p promoted GC progression by suppressing lncRNA HCG11 expression. Besides that, BRMS1 was confirmed as a direct target of miR-942-5p. More importantly, breast cancer metastasis suppressor 1 (BRMS1) inhibited GC progression by upregulating lncRNA HCG11 and downregulating miR-942-5p. In conclusion, LncRNA HCG11 inhibited cell proliferation, migration, and invasion in GC by sponging miR-942-5p and upregulating BRMS1.

scholarly journals Inhibition of Mmp-9 Expression through Nf-Kβ by Natural Compounds as a Possible Therapeutic Adjuvant Strategy in Breast Cancer: A Systematic Review

2019 ◽  
pp. 1-9
Author(s):  
Victor Alves de Oliveira ◽  
Diego Cipriano Chagas ◽  
Jefferson Rodrigues Amorim ◽  
Thaís Rodrigues Nogueira ◽  
Thais Alves Nogueira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Natural Compounds ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Activator Protein 1 ◽  
Mitogen Activated Protein

MMP-9 expression may be induced at the transcriptional level in response to different agents. Due to its fundamental role in cancer progression, the control of MMP expression, especially MMP-9, is the possible target of future adjuvant therapies that seek to reduce metastases and angiogenesis in women with breast cancer. Therefore, the aim of this study was to search in the literature available evidences of extracts/or natural compounds that have potential therapeutic capacity to inhibit MMP-9 expression. Extracts and/or natural compounds identified in this review play a significant role in the inhibition of MMP-9 expression via NF-kβ, and may act on the prevention of metastases from primary breast tumors. The majority of the studies found have shown that natural products are capable of suppressing migration and invasion of breast cancer cells, thus inhibiting the formation of in vitro metastases. Further studies are warranted to understand the potential mechanisms of breast cancer metastasis from signaling cascades intrinsic to the tumor. Moreover, the NF-kβ, followed by Mitogen Activated Protein Kinases / Activator protein 1 (MAPK / AP-1) were the major pathways affected by the extracts and / or compounds studied. These pathways are directly linked to MMP-9 expression.

scholarly journals Vitamin C Inhibits Triple-Negative Breast Cancer Metastasis by Affecting the Expression of YAP1 and Synaptopodin 2

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2997 ◽  
Author(s):  
Liping Gan ◽  
Vladimir Camarena ◽  
Sushmita Mustafi ◽  
Gaofeng Wang
Keyword(s):  
Breast Cancer ◽  
Vitamin C ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Synaptopodin 2

Vitamin C supplementation has been shown to decrease triple-negative breast cancer (TNBC) metastasis. However, the molecular mechanism whereby vitamin C inhibits metastasis remains elusive. It has been postulated that vitamin C reduces the levels of HIF-1α, the master regulator of metastasis, by promoting its hydroxylation and degradation. Here, we show that vitamin C at 100 µM, a concentration achievable in the plasma in vivo by oral administration, blocks TNBC cell migration and invasion in vitro. The protein level of HIF-1α remains largely unchanged in cultured TNBC cells and xenografts, partially due to its upregulated transcription by vitamin C, suggesting that HIF-1α unlikely mediates the action of vitamin C on metastasis. Vitamin C treatment upregulates the expression of synaptopodin 2 and downregulates the expression of the transcription coactivator YAP1, both genes in the Hippo pathway. The changes in SYNPO2 and YAP1 expression were subsequently validated at mRNA and protein levels in cultured TNBC cells and xenografts. Further experiments showed that vitamin C treatment inhibits F-actin assembly and lamellipodia formation, which correlates with the changes in SYNPO2 and YAP1 expression. Overall, these results suggest that vitamin C inhibits TNBC metastasis by affecting the expression of SYNPO2 and YAP1. Vitamin C may thus have a potential role in the prevention and treatment of TNBC metastasis.

scholarly journals Three-Dimensional In Vitro Hydro- and Cryogel-Based Cell-Culture Models for the Study of Breast-Cancer Metastasis to Bone

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 292 ◽  
Author(s):  
Laura Bray ◽  
Constanze Secker ◽  
Berline Murekatete ◽  
Jana Sievers ◽  
Marcus Binner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Cell Function ◽  
Three Dimensional ◽  
Breast Cancer Metastasis ◽  
In Vitro Models ◽  
Cellular Migration ◽  
Breast Tumor Tissue ◽  
Culture Models

Bone is the most common site for breast-cancer invasion and metastasis, and it causes severe morbidity and mortality. A greater understanding of the mechanisms leading to bone-specific metastasis could improve therapeutic strategies and thus improve patient survival. While three-dimensional in vitro culture models provide valuable tools to investigate distinct heterocellular and environmental interactions, sophisticated organ-specific metastasis models are lacking. Previous models used to investigate breast-to-bone metastasis have relied on 2.5D or singular-scaffold methods, constraining the in situ mimicry of in vitro models. Glycosaminoglycan-based gels have demonstrated outstanding potential for tumor-engineering applications. Here, we developed advanced biphasic in vitro microenvironments that mimic breast-tumor tissue (MCF-7 and MDA-MB-231 in a hydrogel) spatially separated with a mineralized bone construct (human primary osteoblasts in a cryogel). These models allow distinct advantages over former models due to the ability to observe and manipulate cellular migration towards a bone construct. The gels allow for the binding of adhesion-mediating peptides and controlled release of signaling molecules. Moreover, mechanical and architectural properties can be tuned to manipulate cell function. These results demonstrate the utility of these biomimetic microenvironment models to investigate heterotypic cell–cell and cell–matrix communications in cancer migration to bone.

scholarly journals Annexin A2 Coordinates STAT3 to Regulate the Invasion and Migration of Colorectal Cancer CellsIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dianhui Xiu ◽  
Lin Liu ◽  
Fengli Qiao ◽  
Haishan Yang ◽  
Lu Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Annexin A2 ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Protein Levels ◽  
And Migration

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.

scholarly journals Screening of a Novel Upregulated lncRNA, A2M-AS1, That Promotes Invasion and Migration and Signifies Poor Prognosis in Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Kai Fang ◽  
Hu Caixia ◽  
Zhang Xiufen ◽  
Guo Zijian ◽  
Lihua Li
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Human Breast ◽  
Free Survival ◽  
Invasion And Migration ◽  
Basal Like Breast Cancer ◽  
And Migration ◽  
Cancer Tissues

Understanding of prognostic factors and therapeutic targets for breast cancer is imperative for guidance of patient care. We studied 1203 tumour samples from the Gene Expression Omnibus (GEO) to evaluate potential genes related to breast cancer. R software was used to analyse differentially expressed long noncoding RNAs (lncRNAs) in the RNA microarray expression profiles GSE45827 and GSE65216 and to identify a series of differentially expressed lncRNAs associated with human breast cancer. Of these lncRNAs, A2M-AS1, a lncRNA that has not been previously reported, was significantly upregulated in human breast cancer tissues compared with adjacent nontumour tissues. Importantly, A2M-AS1 upregulation was significantly associated with ER-negative, HER2-positive, and basal-like breast cancer and with poor recurrence-free survival and metastasis-free survival in breast cancer patients. After validating these results in 96 collected human breast cancer tissues and 64 paired adjacent noncancerous tissues, we further investigated the roles of A2M-AS1 in human ER-negative and basal-like breast cancer cells. The results revealed that A2M-AS1 significantly promotes human breast cancer cell proliferation, invasion, and migration. Additionally, bioinformatics analysis of genes coexpressed with A2M-AS1 in the context of human breast cancer combined with qRT-PCR and Western blot assays revealed that A2M-AS1 exerts regulatory effects on downstream factors in the cell adhesion molecule pathway, including CD2 and SELL. These results imply that A2M-AS1 might be a promising candidate prognostic factor and therapeutic target for breast cancer.

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