Current Knowledge of Long Non-Coding RNA HOTAIR in Breast Cancer Progression and Its Application

Breast cancer is one of the most devastating cancers with high morbidity and mortality in females worldwide. Breast tumorigenesis and further development present great uncertainty and complexity, and efficient therapeutic approaches still lack. Accumulating evidence indicates HOX transcript antisense intergenic RNA (HOTAIR) is dysregulated in cancers and has emerged as a novel hotspot in the field. In breast cancer, aberrant HOTAIR expression is responsible for advanced tumor progression by regulating multifarious signaling pathways. Besides, HOTAIR may act as competitive endogenous RNA to bind to several microRNAs and suppress their expressions, which can subsequently upregulate the levels of targeted downstream messenger RNAs, thereby leading to further cancer progression. In addition, HOTAIR works as a promising biomarker and predictor for breast cancer patients’ diagnosis or outcome prediction. Recently, HOTAIR is potentially considered to be a drug target. Here, we have summarized the induction of HOTAIR in breast cancer and its impacts on cell proliferation, migration, apoptosis, and therapeutic resistance, as well as elucidating the underlying mechanisms. This review aims to provide new insights into investigations between HOTAIR and breast cancer development and inspire new methods for studying the association in depth.

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Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer

10.1101/165068 ◽

2017 ◽

Cited By ~ 2

Author(s):

Lucy Ireland ◽

Almudena Santos ◽

Fiona Campbell ◽

Carlos Figueiredo ◽

Lesley Ellies ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factors ◽

Cancer Progression ◽

Invasive Breast Cancer ◽

Metastatic Breast ◽

Advanced Tumor Stage ◽

Breast Cancer Patients ◽

Advanced Tumor ◽

Potential Biomarker ◽

Insulin Like Growth Factors

ABSTRACTBreast cancer remains the leading cause of cancer death in women due to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumours. 75% of breast cancer patients show activation of Insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in a pre-clinical breast cancer model compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.

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GPER1 and microRNA: Two Players in Breast Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms22010098 ◽

2020 ◽

Vol 22 (1) ◽

pp. 98

Author(s):

Adele Vivacqua

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Target Genes ◽

Current Knowledge ◽

Breast Cancer Progression ◽

Non Coding Rna ◽

Anti Cancer ◽

G Protein Coupled ◽

Breast Tumor Progression

Breast cancer is the main cause of morbidity and mortality in women worldwide. However, the molecular pathogenesis of breast cancer remains poorly defined due to its heterogeneity. Several studies have reported that G Protein-Coupled Estrogen Receptor 1 (GPER1) plays a crucial role in breast cancer progression, by binding to estrogens or synthetic agonists, like G-1, thus modulating genes involved in diverse biological events, such as cell proliferation, migration, apoptosis, and metastasis. In addition, it has been established that the dysregulation of short sequences of non-coding RNA, named microRNAs (miRNAs), is involved in various pathophysiological conditions, including breast cancer. Recent evidence has indicated that estrogens may regulate miRNA expression and therefore modulate the levels of their target genes, not only through the classical estrogen receptors (ERs), but also activating GPER1 signalling, hence suggesting an alternative molecular pathway involved in breast tumor progression. Here, the current knowledge about GPER1 and miRNA action in breast cancer is recapitulated, reporting recent evidence on the liaison of these two players in triggering breast tumorogenic effects. Elucidating the role of GPER1 and miRNAs in breast cancer might provide new tools for innovative approaches in anti-cancer therapy.

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Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery

Life ◽

10.3390/life11090965 ◽

2021 ◽

Vol 11 (9) ◽

pp. 965

Author(s):

Sixuan Li ◽

Hongquan Zhang ◽

Xiaofan Wei

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Drug Targets ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Tumor Development ◽

Ubiquitin Proteasome System ◽

Prognostic Indicators ◽

Breast Cancer Patients ◽

Oncogenic Signaling

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

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Exploring PLAC1 Structure and Underlying Mechanisms to Design a Derivative Vaccine Against Breast Cancer Progression; In-Silico Study

Current Proteomics ◽

10.2174/1570164617666191203111451 ◽

2020 ◽

Vol 17 (5) ◽

pp. 379-391

Author(s):

Farzaneh Afzali ◽

Parisa Ghahremanifard ◽

Mohammad Mehdi Ranjbar ◽

Mahdieh Salimi

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

In Silico ◽

Tertiary Structure ◽

Specific Antigen ◽

Docking Simulation ◽

Post Translational Modification ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Underlying Mechanisms

Background: The tolerogenic homeostasis in Breast Cancer (BC) can be surpassed by rationally designed immune-encouraging constructs against tumor-specific antigens through immunoinformatics approach. Objective: Availability of high throughput data providing the underlying concept of diseases and awarded computational simulations, lead to screening the potential medications and strategies in less time and cost. Despite the extensive effects of Placenta Specific 1 (PLAC1) in BC progression, immune tolerance, invasion, cell cycle regulation, and being a tumor-specific antigen the fundamental mechanisms and regulatory factors were not fully explored. It is also worth to design an immune response inducing construct to surpass the hurdles of traditional anti-cancer treatments. Methods and Result: The study was initiated by predicting and modelling the PLAC1 secondary and tertiary structures and then engineering the fusion pattern of PLAC1 derived immunodominant predicted CD8+ and B-cell epitopes to form a multi-epitope immunogenic construct. The construct was analyzed considering the physiochemical characterization, safety, antigenicity, post-translational modification, solubility, and intrinsically disordered regions. After modelling its tertiary structure, proteinprotein docking simulation was carried out to ensure the attachment of construct with Toll-Like Receptor 4 (TLR4) as an immune receptor. To guarantee the highest expression of the designed construct in E. coli k12 as an expressional host, the codon optimization and in-silico cloning were performed. The PLAC1 related miRNAs in BC were excavated and validated through TCGA BC miRNA-sequencing and databases; the common pathways then were introduced as other probable mechanisms of PLAC1 activity. Conclusion: Regarding the obtained in-silico results, the designed anti-PLAC1 multi-epitope construct can probably trigger humoral and cellular immune responses and inflammatory cascades, therefore may have the potential of halting BC progression and invasion engaging predicted pathways.

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Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽

10.2174/2211536608666190318105757 ◽

2019 ◽

Vol 9 (1) ◽

pp. 58-63

Author(s):

Batool Savari ◽

Sohrab Boozarpour ◽

Maryam Tahmasebi-Birgani ◽

Hossein Sabouri ◽

Seyed Mohammad Hosseini

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Tumor Resection ◽

Tumor Grade ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Serum Samples ◽

Post Surgery ◽

Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

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Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

Endocrine Related Cancer ◽

10.1530/erc-17-0139 ◽

2017 ◽

Vol 24 (10) ◽

pp. R349-R366 ◽

Cited By ~ 19

Author(s):

Catherine Zabkiewicz ◽

Jeyna Resaul ◽

Rachel Hargest ◽

Wen Guo Jiang ◽

Lin Ye

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Bone Morphogenetic Proteins ◽

Therapeutic Potential ◽

Current Knowledge ◽

Breast Tumour ◽

Cellular Functions ◽

Foetal Development ◽

Key Factor ◽

The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

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Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22041918 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1918

Author(s):

Mio Yamaguchi ◽

Kiyoshi Takagi ◽

Koki Narita ◽

Yasuhiro Miki ◽

Yoshiaki Onodera ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Tumor Progression ◽

Tumor Cells ◽

Cancer Progression ◽

Stromal Cells ◽

Human Breast Carcinoma ◽

Breast Cancer Patients ◽

Breast Carcinomas ◽

Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

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Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽

10.3390/antiox10020205 ◽

2021 ◽

Vol 10 (2) ◽

pp. 205

Author(s):

Carmen Griñan-Lison ◽

Jose L. Blaya-Cánovas ◽

Araceli López-Tejada ◽

Marta Ávalos-Moreno ◽

Alba Navarro-Ocón ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cancer Progression ◽

Redox Homeostasis ◽

Breast Carcinogenesis ◽

Breast Cancer Patients ◽

Chemopreventive Agents ◽

Low Degree ◽

Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

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Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer

Scientific Reports ◽

10.1038/s41598-021-93620-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Katsunori Tozuka ◽

Pattama Wongsirisin ◽

Shigenori E. Nagai ◽

Yasuhito Kobayashi ◽

Miki Kanno ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Protein Phosphatase ◽

Protein Phosphatase 2A ◽

Recurrent Breast Cancer ◽

Stage I ◽

Breast Cancer Patients ◽

Potential Biomarker ◽

Phosphatase 2A ◽

Mcf 7

AbstractTo understand the mechanism underlying metastasis, identification of a mechanism-based and common biomarker for circulating tumour cells (CTCs) in heterogenous breast cancer is needed. SET, an endogenous inhibitor of protein phosphatase 2A, was overexpressed in all subtypes of invasive breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60–70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24 breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I–III breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with lymph node metastasis in patients with stage I–III disease. Our results indicate that SET contributes to breast cancer progression and can act as a potential biomarker of CTCs for the detection of metastasis.

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