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

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
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.

scholarly journals The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1212
Author(s):  
Getinet M. Adinew ◽  
Equar Taka ◽  
Patricia Mendonca ◽  
Samia S. Messeha ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Option ◽  
Mesenchymal Transition ◽  
Anticancer Effects

Triple- negative breast cancer (TNBC) incidence rate has regularly risen over the last decades and is expected to increase in the future. Finding novel treatment options with minimum or no toxicity is of great importance in treating or preventing TNBC. Flavonoids are new attractive molecules that might fulfill this promising therapeutic option. Flavonoids have shown many biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In addition to their anticancer effects by arresting the cell cycle, inducing apoptosis, and suppressing cancer cell proliferation, flavonoids can modulate non-coding microRNAs (miRNAs) function. Several preclinical and epidemiological studies indicate the possible therapeutic potential of these compounds. Flavonoids display a unique ability to change miRNAs’ levels via different mechanisms, either by suppressing oncogenic miRNAs or activating oncosuppressor miRNAs or affecting transcriptional, epigenetic miRNA processing in TNBC. Flavonoids are not only involved in the regulation of miRNA-mediated cancer initiation, growth, proliferation, differentiation, invasion, metastasis, and epithelial-to-mesenchymal transition (EMT), but also control miRNAs-mediated biological processes that significantly impact TNBC, such as cell cycle, immune system, mitochondrial dysregulation, modulating signaling pathways, inflammation, and angiogenesis. In this review, we highlighted the role of miRNAs in TNBC cancer progression and the effect of flavonoids on miRNA regulation, emphasizing their anticipated role in the prevention and treatment of TNBC.

scholarly journals Redox Potential of Antioxidants in Cancer Progression and Prevention

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1156
Author(s):  
Sajan George ◽  
Heidi Abrahamse
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Natural Antioxidants ◽  
Redox Balance ◽  
Redox Status ◽  
Enzyme Activation ◽  
Metabolic Reprogramming ◽  
Cellular Functions ◽  
Cellular Redox ◽  
The Right

The benevolent and detrimental effects of antioxidants are much debated in clinical trials and cancer research. Several antioxidant enzymes and molecules are overexpressed in oxidative stress conditions that can damage cellular proteins, lipids, and DNA. Natural antioxidants remove excess free radical intermediates by reducing hydrogen donors or quenching singlet oxygen and delaying oxidative reactions in actively growing cancer cells. These reducing agents have the potential to hinder cancer progression only when administered at the right proportions along with chemo-/radiotherapies. Antioxidants and enzymes affect signal transduction and energy metabolism pathways for the maintenance of cellular redox status. A decline in antioxidant capacity arising from genetic mutations may increase the mitochondrial flux of free radicals resulting in misfiring of cellular signalling pathways. Often, a metabolic reprogramming arising from these mutations in metabolic enzymes leads to the overproduction of so called ’oncometabolites’ in a state of ‘pseudohypoxia’. This can inactivate several of the intracellular molecules involved in epigenetic and redox regulations, thereby increasing oxidative stress giving rise to growth advantages for cancerous cells. Undeniably, these are cell-type and Reactive Oxygen Species (ROS) specific, which is manifested as changes in the enzyme activation, differences in gene expression, cellular functions as well as cell death mechanisms. Photodynamic therapy (PDT) using light-activated photosensitizing molecules that can regulate cellular redox balance in accordance with the changes in endogenous ROS production is a solution for many of these challenges in cancer therapy.

scholarly journals Therapeutic Potential of a Novel αvβ3 Antagonist to Hamper the Aggressiveness of Mesenchymal Triple Negative Breast Cancer Sub-Type

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 139 ◽  
Author(s):  
Billy Hill ◽  
Annachiara Sarnella ◽  
Domenica Capasso ◽  
Daniela Comegna ◽  
Annarita Del Gatto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Migration And Invasion ◽  
Αvβ3 Integrin ◽  
Altered Expression ◽  
Mesenchymal Transition

The mesenchymal sub-type of triple negative breast cancer (MES-TNBC) has a highly aggressive behavior and worse prognosis, due to its invasive and stem-like features, that correlate with metastatic dissemination and resistance to therapies. Furthermore, MES-TNBC is characterized by the expression of molecular markers related to the epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs). The altered expression of αvβ3 integrin has been well established as a driver of cancer progression, stemness, and metastasis. Here, we showed that the high levels of αvβ3 are associated with MES-TNBC and therefore exploited the possibility to target this integrin to reduce the aggressiveness of this carcinoma. To this aim, MES-TNBC cells were treated with a novel peptide, named ψRGDechi, that we recently developed and characterized for its ability to selectively bind and inhibit αvβ3 integrin. Notably, ψRGDechi was able to hamper adhesion, migration, and invasion of MES-TNBC cells, as well as the capability of these cells to form vascular-like structures and mammospheres. In addition, this peptide reversed EMT program inhibits mesenchymal markers. These findings show that targeting αvβ3 integrin by ψRGDechi, it is possible to inhibit some of the malignant properties of MES-TNBC phenotype.

scholarly journals Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1351 ◽  
Author(s):  
Nora Jung ◽  
Veronique Maguer-Satta ◽  
Boris Guyot
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mammary Gland ◽  
Bone Morphogenetic Proteins ◽  
Mammary Gland Development ◽  
Cell Transformation ◽  
Current Knowledge ◽  
Endocrine Disrupting Chemicals ◽  
Normal Mammary Gland ◽  
Gland Development

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA.

scholarly journals Ceramide Metabolism Balance, a Multifaceted Factor in Critical Steps of Breast Cancer Development

2018 ◽  
Vol 19 (9) ◽  
pp. 2527 ◽  
Author(s):  
Victor García-González ◽  
José Díaz-Villanueva ◽  
Octavio Galindo-Hernández ◽  
Israel Martínez-Navarro ◽  
Gustavo Hurtado-Ureta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Chemotherapy Resistance ◽  
Cell Communication ◽  
Low Grade ◽  
Cancer Disease ◽  
Cellular Processes ◽  
Neoplastic Processes ◽  
Key Factor ◽  
Inflammatory State

Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules. Considering the wide biological processes in which sphingolipids are implicated, they have been associated with diseases that present abnormalities in their energetic metabolism, such as breast cancer. In this sense, sphingolipids could modulate various cell features, such as growth, proliferation, survival, senescence, and apoptosis in cancer progression; moreover, ceramide metabolism is associated to chemotherapy resistance, and regulation of metastasis. Cell–cell communication mediated by exosomes and lipoproteins has become relevant in the transport of several sphingolipids. Therefore, in this work we performed a comprehensive analysis of the state of the art about the multifaceted roles of ceramides, specifically the deregulation of ceramide metabolism pathways, being a key factor that could modulate neoplastic processes development. Under specific conditions, sphingolipids perform important functions in several cellular processes, and depending on the preponderant species and cellular and/or tissue status can inhibit or promote the development of metabolic and potentially breast cancer disease.

scholarly journals Phosphorylation of ERα at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ERα phosphorylation in breast cancer progression

2006 ◽  
Vol 13 (3) ◽  
pp. 851-861 ◽  
Author(s):  
N Sarwar ◽  
J-S Kim ◽  
J Jiang ◽  
D Peston ◽  
H D Sinnett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Endocrine Resistance ◽  
Breast Tumour ◽  
Good Prognosis ◽  
Tamoxifen Treatment ◽  
Independent Manner ◽  
Previously Treated ◽  
Pre Treatment

Oestrogen receptor-α (ERα) is an important prognostic marker in breast cancer and endocrine therapies are designed to inhibit or prevent ERα activity. In vitro studies have indicated that phosphorylation of ERα, in particular on serine 118 (S118), can result in activation in a ligand-independent manner, thereby potentially contributing to resistance to endocrine agents, such as tamoxifen and aromatase inhibitors. Here we report the immunohistochemistry (IHC) of S118 phosphorylation in 301 primary breast tumour biopsies. Surprisingly, this analysis shows that S118 phosphorylation is higher in more differentiated tumours, suggesting that phosphorylation at this site is associated with a good prognosis in patients not previously treated with endocrine agents. However, we also report that S118 phosphorylation was elevated in tumour biopsies taken from patients who had relapsed following tamoxifen treatment, when compared to pre-treatment biopsies. Taken together, these data are consistent with the view that S118 phosphorylation is a feature of normal ERα function and that increases in levels of phosphorylation at this site may play a key role in the emergence of endocrine resistance in breast cancer.

scholarly journals Embryonic Protein NODAL Regulates the Breast Tumour Microenvironment by Reprogramming Cancer-Derived Secretomes

2020 ◽  
Author(s):  
Dylan Dieters-Castator ◽  
Paola Marino Dantonio ◽  
Matt Piaseczny ◽  
Guihua Zhang ◽  
Jiahui Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Triple Negative ◽  
Breast Tumour ◽  
Tumour Microenvironment ◽  
Breast Cancers ◽  
Dynamic Regulation ◽  
Important Mediator ◽  
Activated Fibroblasts

AbstractThe tumour microenvironment (TME) is an important mediator of breast cancer progression. Cancer-associated fibroblasts (CAFs) constitute a major component of the TME and may originate from tissue-associated fibroblasts or infiltrating mesenchymal stromal cells (MSCs). The mechanisms by which cancer cells activate fibroblasts and recruit MSCs to the TME are largely unknown, but likely include deposition of a pro-tumourigenic secretome. The secreted embryonic protein NODAL is clinically associated with breast cancer stage and promotes tumour growth, metastasis, and vascularization. Herein, we show that NODAL expression correlates with the presence of activated fibroblasts in human triple negative breast cancers and that it directly induces CAF phenotypes. We further show that NODAL reprograms cancer cell secretomes by simultaneously altering levels of chemokines (e.g. CXCL1), cytokines (e.g. IL-6) and growth factors (e.g. PDGFRA), leading to alterations in MSC chemotaxis. We therefore demonstrate a hitherto unappreciated mechanism underlying the dynamic regulation of the TME.

scholarly journals Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 79
Author(s):  
Getinet M. Adinew ◽  
Equar Taka ◽  
Bereket Mochona ◽  
Ramesh B Badisa ◽  
Elizabeth A Mazzio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Advanced Tumor ◽  
Uncontrolled Cell Proliferation

To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system. Various cellular components of the TME work together to drive cancer processes, some of which include tumor-associated adipocytes, fibroblasts, macrophages, and neutrophils which sustain perpetual amplification and release of pro-inflammatory molecules such as cytokines. Thymoquinone (TQ), a natural chemical component from black cumin seed, is widely used traditionally and now in clinical trials for the treatment/prevention of multiple types of cancer, showing a potential to mitigate components of TME at various stages by various pathways. In this review, we focus on the role of TME in TNBC cancer progression and the effect of TQ on the TME, emphasizing their anticipated role in the prevention and treatment of TNBC. It was concluded from this review that the multiple components of the TME serve as a critical part of TNBC tumor promotion and stimulation of uncontrolled cell proliferation. Meanwhile, TQ could be a crucial compound in the prevention and progression of TNBC therapy through the modulation of the TME.

scholarly journals Efficient Synergistic Combination Effect of Endurance Exercise with Curcumin on Breast Cancer Progression Through Inflammatory Pathway Inhibition in BALB/C Mice

2021 ◽  
Author(s):  
Maryam Delfan ◽  
Fatemeh Ramzi
Keyword(s):  
Breast Cancer ◽  
Endurance Training ◽  
Cancer Progression ◽  
Endurance Exercise ◽  
Significant Decline ◽  
Breast Cancer Progression ◽  
Combination Effect ◽  
Tnf Α ◽  
Synergistic Combination ◽  
The Right

Introduction: TNF-α/NF-kB signaling pathway plays an important role in promoting the inflammatory process and growth of breast cancer. Accordingly, the aim of the present study was to investigate the synergistic combination effect of endurance exercise with curcumin on breast cancer progression through TNF-α/NF-kB signaling axes in female BALB/c mice with breast cancer. Methods: The design of the present study was experimental. After transplanting 4T1 breast cancer into the right flank of 40 BALB/c mice, all mice were randomly divided into four groups, including endurance training (E), endurance training-curcumin (EC), curcumin (CC), and control (C). Then, E and EC groups (5 days per week) were performed for 5 weeks. Curcumin (6 times per week) was given by gavage to EC and CC groups for five weeks. The intratumoral expression of TNF-α and NF-kβ were measured using the qRT-PCR method. One-way analysis of variance and LSD post hoc test with SPSS version 16 were used for statistical analysis. P< 0.05 was considered statistically significant. Results: A significant decline in cancer growth and the gene expression of NF-kβ and TNF-α was observed in E, CC, and EC compared to the C group (P =0.001). Furthermore, a significant decline in expression of both genes was observed in EC compared with E. Conclusion: Endurance training combined with curcumin supplementation has a more effective role in reducing TNF-α and NF-κβ, and slowing the growth of breast cancer cells when compared with either of other interventions alone.

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