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Topic Review
SHED-Dependent Oncogenic Signaling of the PEAK3 Pseudo-Kinase
The human kinome is composed of about 50 pseudo-kinases with unclear function, because they are predicted to be catalytically inactive; however, they are shown to play an important role in cancer, similar to active kinases. Understanding how these pseudo-kinases promote tumor formation despite their catalytic inactivity is a great challenge, which may lead to innovative anti-cancer therapies. The PEAK1 and 2 pseudo-kinases have emerged as important components of the protein tyrosine kinase pathway implicated in cancer progression. They can signal using a scaffolding mechanism via a conserved split helical dimerization (SHED) module.
  • 749
  • 11 Jan 2022
Topic Review
Iron, Ferroptosis, and Head and Neck Cancer
Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. 
  • 748
  • 20 Oct 2023
Topic Review
Oxidative Stress and Laminopathies Caused by LMNA Mutations
Mutations in the genes that encode for lamins, predominantly lamin A/C, cause a wide spectrum of human diseases, referred to as laminopathies, including muscular dystrophy, lipodystrophy, and systemic premature aging syndrome. HGPS, one of the most severe laminopathies, is a rare genetic disorder characterized by multisystem abnormalities, including premature aging. The most frequent mutation causing HGPS is c.1842C>T (p.G608G) in exon 11 of LMNA, resulting in cryptic splicing between an abnormal donor site in the middle of exon 11 and the usual acceptor of exon 12. This change causes a 50-amino acid deletion in the carboxyl-terminal tail of prelamin A, producing a truncated protein referred to as progerin. The 50 missing amino acids include the recognition sites for the prelamin A-cleaving enzyme ZMPSTE24. Consequently, progerin is normally farnesylated but cannot be further processed because of the lack of docking sites for ZMPSTE24. The farnesylated domain of progerin is firmly anchored to the nuclear membrane, leading to nuclear deformation and deleterious effects in HGPS cells. Blocking the farnesylation of progerin with a farnesyltransferase inhibitor (FTI) successfully reduced the cytotoxic effects of progerin in vitro; however, a clinical trial of FTIs did not yield promising results. A study showed that the interaction between progerin and wild-type lamin A/C was also a critical cause of nuclear deformation in HGPS and normal aging cells, providing a new therapeutic target for HGPS. Progerin expression in various cell types induces excessive ROS production and reduces the activities of the antioxidant system. Oxidative stress is also implicated in other types of laminopathies, such as Dunnigan-type familial partial lipodystrophy (FPLD), amyotrophic quadricipital syndrome with cardiac involvement, autosomal dominant Emery–Dreifuss muscular dystrophy (AD-EDMD), and restrictive dermopathy (RD).
  • 747
  • 25 May 2023
Topic Review
Biology of NSCLC
The overall prognosis and survival of non-small cell lung cancer (NSCLC) patients remain poor. The immune system plays an integral role in driving tumor control, tumor progression, and overall survival of NSCLC patients. While the tumor cells possess many ways to escape the immune system, conventional radiotherapy (RT) approaches, which are directly cytotoxic to tumors, can further add additional immune suppression to the tumor microenvironment by destroying many of the lymphocytes that circulate within the irradiated tumor environment.
  • 746
  • 26 Feb 2021
Topic Review
Role of Interleukin-11 in Non-Small Cell Lung Cancer
Interleukin-11 (IL11), a stromal-cell derived pleiotropic cytokine with profibrotic and cellular remodeling properties, as a potential biomarker in non-small cell lung cancer (NSCLC). IL11 is an important tumor-promoting cytokine that that has both diagnostic and prognostic value in patients with NSCLC. Multiple in vitro studies confirm that IL11 activates known tumor-promoting signaling pathways and clinical studies link increased IL11 expression to poorer prognosis. 
  • 746
  • 22 Aug 2022
Topic Review
ATP12A Proton Pump in Respiratory Diseases
ATP12A encodes the catalytic subunit of the non-gastric proton pump, which is expressed in many epithelial tissues and mediates the secretion of protons in exchange for potassium ions. In the airways, ATP12A-dependent proton secretion contributes to complex mechanisms regulating the composition and properties of the fluid and mucus lining the respiratory epithelia, which are essential to maintain the airway host defense and the respiratory health. Increased expression and activity of ATP12A in combination with the loss of other balancing activities, such as the bicarbonate secretion mediated by CFTR, leads to excessive acidification of the airway surface liquid and mucus dysfunction, processes that play relevant roles in the pathogenesis of cystic fibrosis and other chronic inflammatory respiratory disorders. Here, the researchers summarize the findings dealing with ATP12A expression, function, and modulation in the airways, which led to the consideration of ATP12A as a potential therapeutic target for the treatment of cystic fibrosis and other airway diseases; the researchers also highlight the current advances and gaps regarding the development of therapeutic strategies aimed at ATP12A inhibition.
  • 746
  • 18 Oct 2023
Topic Review
BCR::ABL1-Negative MPN
Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell-derived disorders characterized by uncontrolled proliferation of differentiated myeloid cells. Two main groups of MPN, BCR::ABL1-positive (Chronic Myeloid Leukemia) and BCR::ABL1-negative (Polycythemia Vera, Essential Thrombocytosis, Primary Myelofibrosis) are distinguished. For many years, cytomorphologic and histologic features were the only proof of MPN and attempted to distinguish the different entities of the subgroup BCR::ABL1-negative MPN. World Health Organization (WHO) classification of myeloid neoplasms evolves over the years and increasingly considers molecular abnormalities to prove the clonal hematopoiesis.
  • 745
  • 31 Mar 2023
Topic Review
Next-Generation Sequencing in Acute Myeloid Leukemia
Cytological approaches have long been used in the diagnosis, prognosis, and management of acute myeloid leukemia (AML) and myelodysplastic neoplasms. Technological advances in molecular biology, in particular next-generation sequencing (NGS), have made it possible to establish a molecular list of several gene mutations in AML and MDS, within a matter of days.
  • 744
  • 10 Jul 2023
Topic Review
New Vulnerabilities of Melanoma
Melanoma cells are notorious for their high plasticity and ability to switch back and forth between various melanoma cell states, enabling the adaptation to sub-optimal conditions and therapeutics. This phenotypic plasticity, which has gained more attention in cancer research, is proposed as a new paradigm for melanoma progression. Here the researchers present several rational therapeutic approaches, such as exploiting phenotype-specific and metabolic vulnerabilities and targeting components and signals of the tumor microenvironment (TME), to improve the response of melanoma patients to treatments.
  • 743
  • 13 Apr 2022
Topic Review
Mesenchymal Stem Cells-Based Cell-Free Therapy in Wound Healing
A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, and re-modeling. Factors such as infection, ischemia, and chronic diseases such as diabetes can compromise wound healing, leading to chronic and refractory ulcers. Mesenchymal stem cells (MSCs) have been used to treat various wound models due to their paracrine activity (secretome) and extracellular vehicles (exosomes) that contain several molecules, including long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, and lipids. Studies have shown that MSCs-based cell-free therapy using secretome and exosomes has great potential in regenerative medicine compared to MSCs, as there are fewer safety concerns.
  • 742
  • 07 Jun 2023
Topic Review
Implications of Phosphatase and Tensin Homolog in NSCLC
Lung cancer remains one of the major human malignancies affecting both men and women worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent type. Multiple mechanisms have been identified that favor tumor growth as well as impede the efficacy of therapeutic regimens in lung cancer patients. Among tumor suppressor genes that play critical roles in regulating cancer growth, the phosphatase and tensin homolog (PTEN) constitutes one of the important family members implicated in controlling various functional activities of tumor cells, including cell proliferation, apoptosis, angiogenesis, and metastasis.
  • 742
  • 29 Aug 2023
Topic Review
Neoangiogenesis and Extracellular Matrix of HNSCC
Head and neck squamous cell cancer (HNSCC) is one of the ten most common malignant neoplasms, characterized by an aggressive course, high recurrence rate, poor response to treatment, and low survival rate. This creates the need for a deeper understanding of the mechanisms of the pathogenesis of this cancer. The tumor microenvironment (TME) of HNSCC consists of stromal and immune cells, blood and lymphatic vessels, and extracellular matrix. It is known that HNSCC is characterized by complex relationships between cancer cells and TME components. TME components and their dynamic interactions with cancer cells enhance tumor adaptation to the environment, which provides the highly aggressive potential of HNSCC and resistance to antitumor therapy.
  • 740
  • 30 Nov 2023
Topic Review
FRA-1 as a Regulator in Breast Cancer
Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by FOSL1) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which FOSL1 is overexpressed in the TNBC (Triple Negative Breast Cancer)/basal subtypes, correlates with the FRA-1-dependent transcriptional regulation of EMT (Epithelial-to-Mesenchymal Transition).
  • 740
  • 21 Jun 2023
Topic Review
Sexual Dimorphism in Interstitial Lung Disease
Interstitial lung diseases (ILD) are a group of heterogeneous progressive pulmonary disorders, characterised by tissue remodelling and/or fibrotic scarring of the lung parenchyma. ILD patients experience lung function decline with progressive symptoms, poor response to treatment, reduced quality of life and high mortality. ILD can be idiopathic or associated with systemic or connective tissue diseases (CTD) but idiopathic pulmonary fibrosis (IPF) is the most common form. While IPF has a male predominance, women are affected more greatly by CTD and therefore associated ILDs. The mechanisms behind biological sex differences in these progressive lung diseases remain unclear. However, differences in environmental exposures, variable expression of X-chromosome related inflammatory genes and sex hormones play a role.
  • 739
  • 08 Feb 2023
Topic Review
The Functions of NRF2 in Carcinogenesis and Cancer
The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2)-KEAP1 system is the master regulator of cellular redox and metabolic homeostasis. NRF2 has Janus-like roles in carcinogenesis and cancer development. Short-term NRF2 activation suppresses tissue injury, inflammation, and cancer initiation.
  • 739
  • 19 May 2023
Topic Review
MicroRNA in Cervical Lesions
The regulatory functions of microRNA (miRNA) are involved in all processes contributing to carcinogenesis and response to viral infections. Cervical cancer in most cases is caused by the persistence of high-risk human papillomavirus (HR-HPV) infection. While oncogenic human papillomaviruses induce aberrant expression of many cellular miRNAs, this dysregulation could be harnessed as a marker in early diagnosis of HR-HPV infection, cervical squamous intraepithelial lesions, and cancer. In recent years, growing data indicate that miRNAs show specific patterns at various stages of cervical pathology, that gives hope for the development of non-invasive diagnostic tests that take into account the heterogeneity of tumor-related changes. Due to this heterogeneity resulting in difficult to predict clinical outcomes, precise molecular tools are needed to improve the diagnostic and therapeutic process.
  • 738
  • 30 Nov 2020
Topic Review
Galectin-16 Gene in Human Cells and Tissues
Galectins are soluble β-galactoside binding proteins, which are involved in regulation of multiple cellular processes including cell growth, differentiation, apoptosis, and immune responses. Sixteen galectin genes have been identified in animals, 12 of which are expressed in humans. Out of all galectins, galectin-16 is poorly characterized yet and current knowledge suggest that this is a tissue-specific gene with functions and expression limited to placenta and brain among others.
  • 737
  • 06 Jun 2022
Topic Review
BRAF and MEK Inhibitors in Pediatric CNS Tumors
BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics.
  • 737
  • 13 Sep 2022
Topic Review
Functional Effects of TGF-β3
Transforming growth factor-beta 3 (TGF-β3) is a ubiquitously expressed multifunctional cytokine involved in a range of physiological and pathological conditions, including embryogenesis, cell cycle regulation, immunoregulation, and fibrogenesis. 
  • 737
  • 10 May 2023
Topic Review
Hypoxia-Inducible Factors and Immunosenescence
Hypoxia activates hypoxia-related signaling pathways controlled by hypoxia-inducible factors (HIFs). HIFs represent a quick and effective detection system involved in the cellular response to insufficient oxygen concentration.
  • 737
  • 23 Aug 2023
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