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Topic Review
BRCA1 and Metastasis: Outcome of Defective DNA Repair
BRCA1 has critical functions in accurately repairing double stand breaks in the DNA through a process known as homologous recombination. BRCA1 also has various functions in other cellular processes that safeguard the genome. Thus, mutations or silencing of this tumor suppressor significantly increases the risk of developing breast, ovarian, and other cancers. The objective of this review is to provide significant insights into the mechanisms by which BRCA1 mutations contribute to the metastatic and aggressive nature of the tumor cells. 
  • 312
  • 07 Jan 2022
Topic Review
BRCA1 in Centrosome Regulation
Breast cancer gene 1 (BRCA1) is a tumor suppressor associated with hereditary breast and ovarian cancer and forms a heterodimer with BRCA1-associated RING domain protein 1 (BARD1). Centrosomes are the major microtubule-organizing centers in animal cells and are critical for the formation of a bipolar mitotic spindle. BRCA1 and BARD1 localize to the centrosome during the cell cycle, and the BRCA1/BARD1 dimer ubiquitinates centrosomal proteins to regulate centrosome function.
  • 662
  • 03 Aug 2020
Topic Review
Breakdown of Filamentous Myofibrils
Protein degradation maintains cellular integrity by regulating virtually all biological pro- cesses, whereas impaired proteolysis perturbs protein quality control, and often leads to human disease. Two major proteolytic systems are responsible for protein breakdown in all cells: autophagy, which facilitates the loss of organelles, protein aggregates, and cell surface proteins; and the ubiquitin-proteasome system (UPS), which promotes degradation of mainly soluble proteins. Recent findings indicate that more complex protein structures, such as filamentous assemblies, which are not acces- sible to the catalytic core of the proteasome in vitro, can be efficiently degraded by this proteolytic machinery in systemic catabolic states in vivo. Mechanisms that loosen the filamentous structure seem to be activated first, hence increasing the accessibility of protein constituents to the UPS. In this review, we will discuss the mechanisms underlying the disassembly and loss of the intricate insoluble filamentous myofibrils, which are responsible for muscle contraction, and whose degradation by the UPS causes weakness and disability in aging and disease. Several lines of evidence indicate that myofibril breakdown occurs in a strictly ordered and controlled manner, and the function of AAA-ATPases is crucial for their disassembly and loss.
  • 586
  • 30 Apr 2021
Topic Review
Breast cancer cell growth/motility is influenced by metal compounds
Triple-negative breast cancer (TNBC) is a  highly "aggressive" malignant neoplasm with limited treatment options due to the lack of expression of estrogen and progesterone receptors and HER2/neu. In search of novel molecules displaying anti-TNBC activities, the TNBC cell line MDA-MB231 was exposed to cadmium chloride and/or manganese chloride, and a biological characterization of the effect observed was performed. The data obtained demonstrate a cytotoxic effect exerted by cadmium chloride with drastic changes affecting gene expressions and production of reactive oxygen species. Conversely, manganese chloride was effective in increasing cell number and promoting cell invasive ability.  Such effect was reverted by coexposure with cadmium chloride. Thus, metal compounds appear to be able to modulate the biological behavior of TNBC cells, although addressing them to different fates. The data obtained suggest that high environmental pollution with manganese chloride might increase the risk of breast tumorigenesis. On the other hand, the restraining modulatory property of cadmium chloride looks promising and deserves a more detailed mechanistic study aimed to the identification of possible molecular targets instrumental in inhibiting the expansion of malignant breast cancer.
  • 1.3K
  • 30 Oct 2020
Topic Review
Breast Cancer Management and Extracellular Vesicle Research
Extracellular vesicles are lipid bilayer-enclosed particles released from all types of cells and found in biological fluids, which transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, the study aimed to investigate the trends in breast cancer management involved with extracellular vesicle research.
  • 466
  • 23 Nov 2021
Topic Review
Breast Cancer Metastasis Studying Tool
During the metastatic process, breast cancer cells must come into contact with the extra-cellular matrix (ECM) at every step. The ECM provides both structural support and biochemical cues, and cell–ECM interactions can lead to changes in drug response. Here, we used fibroblast-derived ECM (FDM) to perform high throughput drug screening of 4T1 breast cancer cells on metastatic organ ECM (lung), and we see that drug response differs from treatment on plastic. The FDMs that we can produce from different organs are abundant in and contains a complex mixture of ECM proteins. We also show differences in ECM composition between the primary site and secondary organ sites. Furthermore, we show that global kinase signalling of 4T1 cells on the ECM is relatively unchanged between organs, while changes in signalling compared to plastic are significant. Our study highlights the importance of context when testing drug response in vitro, showing that consideration of the ECM is critically important. 
  • 425
  • 06 Jul 2021
Topic Review
Breast carcinoma eukaryotic initiation factors
Breast cancer is the most frequent neoplasm in females. It is a heterogenous entity, classified into intrinsic subtypes based on gene expression data and in corresponding clinical subtypes based on the determination of hormone receptor expression and proliferative activity estimated from ki67 by immunohistochemistry. As for other tumors, the metabolism of breast tumors depends on aerobic glycolysis ("Warburg-effect") and the capability for effective biosynthesis of proteins. Quantity and quality of protein biosynthesis is mainly controlled in the initiation phase of translation, which is characterized by a complex interaction of eucaryotic initiation factors with the mRNA and ribosomal proteins to form a translationally active ribosome. Thus the eIF subunit composition varies from cancer to cancer and is a key factor for determining the cancer cell´s proteome. eIFs can therefore become a suitable anti-cancer drug target. We here summarize the current knowledge on eIF expression and prognostic impact in breast cancer.
  • 512
  • 11 Aug 2020
Topic Review
Bromodomain Proteins in Cancer
This review provides an in depth analysis of the role of bromodomain-containing proteins in cancer development. As readers of acetylated lysine on nucleosomal histones, bromodomain proteins are poised to activate gene expression, and often promote cancer progression. We examined changes in gene expression patterns that are observed in bromodomain-containing proteins and associated with specific cancer types. We also mapped the protein–protein interaction network for the human bromodomain-containing proteins, discuss the cellular roles of these epigenetic regulators as part of nine different functional groups, and identify bromodomain-specific mechanisms in cancer development. Lastly, we summarize emerging strategies to target bromodomain proteins in cancer therapy, including those that may be essential for overcoming resistance. Overall, this review provides a timely discussion of the different mechanisms of bromodomain-containing proteins in cancer, and an updated assessment of their utility as a therapeutic target for a variety of cancer subtypes.
  • 537
  • 07 Aug 2021
Topic Review
Bronchopulmonary dysplasia-associated pulmonary hypertension
       Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting preterm infants. More than 50 years after the first description of BPD by Northway, this chronic lung disease affecting many preterm infants is still less understood. Additonally, approximately 40% of preterm infants suffering from severe BPD also suffer from Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH), leading to a significant increase in total morbidity and mortality. Until today, there is no curative therapy for both BPD and BPD-PH available. It has become increasingly evident that growth factors are playing a central role in normal and pathologic development of the pulmonary vasculature. Thus, this review aims to summarize the recent evidence in our understanding of BPD-PH from a basic scientific point of view, focusing on the potential role of Fibroblast Growth Factor (FGF)/FGF10 signaling pathway contributing to disease development, progression and resolution.
  • 1.0K
  • 26 Aug 2020
Topic Review
Brown Adipose Tissue Architecture and Thermogenic Function
The body of mammals harbors two distinct types of adipose tissue: While cells within the white adipose tissue (WAT) store surplus energy as lipids, brown adipose tissue (BAT) is nowadays recognized as the main tissue for transforming chemical energy into heat. This process, referred to as ‘non-shivering thermogenesis’, is facilitated by the uncoupling of the electron transport across mitochondrial membranes from ATP production. BAT-dependent thermogenesis acts as a safeguarding mechanism under reduced ambient temperature but also plays a critical role in metabolic and energy homeostasis in health and disease. 
  • 495
  • 19 Dec 2022
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