scholarly journals Primary Cilium in Cancer Hallmarks

2019 ◽  
Vol 20 (6) ◽  
pp. 1336 ◽  
Author(s):  
Lucilla Fabbri ◽  
Frédéric Bost ◽  
Nathalie Mazure
Keyword(s):  
Cancer Progression ◽  
Primary Cilium ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Cancer Hallmarks ◽  
Mutual Regulation ◽  
Ultrastructure And Function ◽  
And Function ◽  
External Stimuli

The primary cilium is a solitary, nonmotile and transitory appendage that is present in virtually all mammalian cells. Our knowledge of its ultrastructure and function is the result of more than fifty years of research that has dramatically changed our perspectives on the primary cilium. The mutual regulation between ciliogenesis and the cell cycle is now well-recognized, as well as the function of the primary cilium as a cellular “antenna” for perceiving external stimuli, such as light, odorants, and fluids. By displaying receptors and signaling molecules, the primary cilium is also a key coordinator of signaling pathways that converts extracellular cues into cellular responses. Given its critical tasks, any defects in primary cilium formation or function lead to a wide spectrum of diseases collectively called “ciliopathies”. An emerging role of primary cilium is in the regulation of cancer development. In this review, we seek to describe the current knowledge about the influence of the primary cilium in cancer progression, with a focus on some of the events that cancers need to face to sustain survival and growth in hypoxic microenvironment: the cancer hallmarks.

scholarly journals Lysosomal Biology and Function: Modern View of Cellular Debris Bin

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1131 ◽  
Author(s):  
Purvi C. Trivedi ◽  
Jordan J. Bartlett ◽  
Thomas Pulinilkunnil
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Site Formation ◽  
Cellular Debris ◽  
Vesicular Membrane ◽  
Nutrient Signaling ◽  
Membrane Contact ◽  
And Function ◽  
Chaperone Mediated Autophagy

Lysosomes are the main proteolytic compartments of mammalian cells comprising of a battery of hydrolases. Lysosomes dispose and recycle extracellular or intracellular macromolecules by fusing with endosomes or autophagosomes through specific waste clearance processes such as chaperone-mediated autophagy or microautophagy. The proteolytic end product is transported out of lysosomes via transporters or vesicular membrane trafficking. Recent studies have demonstrated lysosomes as a signaling node which sense, adapt and respond to changes in substrate metabolism to maintain cellular function. Lysosomal dysfunction not only influence pathways mediating membrane trafficking that culminate in the lysosome but also govern metabolic and signaling processes regulating protein sorting and targeting. In this review, we describe the current knowledge of lysosome in influencing sorting and nutrient signaling. We further present a mechanistic overview of intra-lysosomal processes, along with extra-lysosomal processes, governing lysosomal fusion and fission, exocytosis, positioning and membrane contact site formation. This review compiles existing knowledge in the field of lysosomal biology by describing various lysosomal events necessary to maintain cellular homeostasis facilitating development of therapies maintaining lysosomal function.

scholarly journals How Hippo Signaling Pathway Modulates Cardiovascular Development and Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Wenyi Zhou ◽  
Mingyi Zhao
Keyword(s):  
Cardiovascular Disease ◽  
Tumor Suppressor ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Cardiovascular Development ◽  
Molecular Therapeutic ◽  
And Function

Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway. YAP, the core effecter of the Hippo pathway, may accumulate in the nucleus and initiate transcriptional activity if the pathway is inhibited. The role of Hippo signaling has been widely investigated in organ development and cancers. A heart of normal size and function which is critical for survival could not be generated without the proper regulation of the Hippo tumor suppressor pathway. Recent research has demonstrated a novel role of Hippo signaling in cardiovascular disease in the context of development, hypertrophy, angiogenesis, regeneration, apoptosis, and autophagy. In this review, we summarize the current knowledge of how Hippo signaling modulates pathological processes in cardiovascular disease and discuss potential molecular therapeutic targets.

scholarly journals Molecular pathology of prostate cancer: the key to identifying new biomarkers of disease

2004 ◽  
Vol 11 (3) ◽  
pp. 477-488 ◽  
Author(s):  
Ruth Foley ◽  
Donal Hollywood ◽  
Mark Lawler
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Molecular Pathology ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Point Mutations ◽  
Androgen Independence ◽  
Molecular Events ◽  
New Biomarkers ◽  
And Function

Microarray technology has recently accelerated the study of the molecular events involved in prostate cancer, offering the prospect of more precise prognosis and new therapeutic strategies. This review summarises current knowledge of the molecular pathology of prostate cancer. The expression and function of numerous genes have been shown to be altered in prostate cancer. Many of these genes are involved in cell cycle regulation, steroid hormone metabolism or regulation of gene expression. The mechanisms by which androgen independence arises are discussed, including cross-activation, gene amplification and point mutations of the androgen receptor. Analysis of changes in the levels of expression of large numbers of genes during prostate cancer progression have provided a better understanding of the basis of the disease, yielding new molecular markers, such as hepsin, with potential use in diagnosis and prognosis.

scholarly journals Extracellular Vesicles in Cervical Cancer and HPV Infection

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 453
Author(s):  
Víctor Acevedo-Sánchez ◽  
Ruth M. Rodríguez-Hernández ◽  
Sergio R. Aguilar-Ruíz ◽  
Honorio Torres-Aguilar ◽  
María de los A. Romero-Tlalolini
Keyword(s):  
Cervical Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Hpv Infection ◽  
Dna And Rna ◽  
Cell Structures ◽  
Infected Cells ◽  
And Function ◽  
Oncogenic Protein

Since their description, extracellular vesicles (EVs) have shown growing relevance in cancer progression. These cell structures contain and transfer molecules such as nucleic acids (including DNA and RNA), proteins, and lipids. Despite the rising information about EVs’ relationship with cancer, there is still scarce evidence about their content and function in cervical cancer. Interestingly, the composition and purposes of some cellular molecules and the expression of oncogenic proteins packaged in EVs seem modified in HPV-infected cells; and, although only the E6 oncogenic protein has been detected in exosomes from HPV-positive cells, both E6/E7 oncogenes mRNA has been identified in EVs; however, their role still needs to be clarified. Given that EVs internalizing into adjacent or distant cells could modify their cellular behavior or promote cancer-associated events like apoptosis, proliferation, migration, or angiogenesis in receptor cells, their comprehensive study will reveal EV-associated mechanisms in cervical cancer. This review summarizes the current knowledge in composition and functions of cervical cancer and HPV Infection-derived EVs.

scholarly journals Nanobody-directed targeting of optogenetic tools to study signaling in the primary cilium

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jan N Hansen ◽  
Fabian Kaiser ◽  
Christina Klausen ◽  
Birthe Stüven ◽  
Raymond Chong ◽  
...  
Keyword(s):  
Primary Cilium ◽  
Protein Function ◽  
Mammalian Cells ◽  
Camp Signaling ◽  
Subcellular Compartment ◽  
Cellular Behavior ◽  
Health And Disease ◽  
And Function ◽  
Ciliary Signaling

Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. The primary cilium constitutes a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling has been challenging due to the lack of tools to investigate ciliary signaling. Here, we describe a nanobody-based targeting approach for optogenetic tools in mammalian cells and in vivo in zebrafish to specifically analyze ciliary signaling and function. Thereby, we overcome the loss of protein function observed after fusion to ciliary targeting sequences. We functionally localized modifiers of cAMP signaling, the photo-activated adenylyl cyclase bPAC and the light-activated phosphodiesterase LAPD, and the cAMP biosensor mlCNBD-FRET to the cilium. Using this approach, we studied the contribution of spatial cAMP signaling in controlling cilia length. Combining optogenetics with nanobody-based targeting will pave the way to the molecular understanding of ciliary function in health and disease.

scholarly journals ENKD1 is a centrosomal and ciliary microtubule-associated protein important for primary cilium assembly and Hedgehog signaling

2021 ◽  
Author(s):  
Fatmanur Tiryaki ◽  
Jovana Deretic ◽  
Elif Nur Firat-Karalar
Keyword(s):  
Primary Cilium ◽  
Mammalian Cells ◽  
Hedgehog Signaling ◽  
Developmental Disorders ◽  
Cell Function ◽  
Microtubule Organization ◽  
Regulatory Relationship ◽  
Cellular Assays ◽  
And Function

Centrioles and cilia are conserved, microtubule-based structures critical for cell function and development. Their structural and functional defects cause cancer and developmental disorders. How microtubules are organized into ordered structures by microtubule-associated proteins (MAPs) and tubulin modifications is best understood during mitosis but is largely unexplored for the centrioles and the ciliary axoneme, which are composed of remarkably stable microtubules that maintain their length at steady state. In particular, we know little about the identity of the centriolar and ciliary MAPs and how they work together during the assembly and maintenance of the cilium and centriole. Here, we identified Enkurin domain containing 1 (ENKD1) as a component of the centriole wall and the axoneme in mammalian cells, and showed that it has extensive proximity interactions with these compartments and MAPs. Using in vitro and cellular assays, we found that ENKD1 is a new MAP that promotes microtubule polymerization and regulates microtubule organization and stability. Consistently, overexpression of ENKD1 increased tubulin polymerization and acetylation and disrupted microtubule organization. Cells depleted for ENKD1 were defective in ciliary length and content regulation and failed to respond to Hedgehog pathway activation. Together, our results establish ENKD1 as a new centriolar and ciliary MAP that regulate primary cilium structure and function, and advances our understanding of the functional and regulatory relationship between MAPs and the primary cilium.

scholarly journals The Role of Centrosome Distal Appendage Proteins (DAPs) in Nephronophthisis and Ciliogenesis

2021 ◽  
Vol 22 (22) ◽  
pp. 12253
Author(s):  
Fatma Mansour ◽  
Felix J. Boivin ◽  
Iman B. Shaheed ◽  
Markus Schueler ◽  
Kai M. Schmidt-Ott
Keyword(s):  
Primary Cilium ◽  
Mammalian Cells ◽  
Vital Role ◽  
Vesicle Docking ◽  
Genes Encoding ◽  
Mother Centriole ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function

The primary cilium is found in most mammalian cells and plays a functional role in tissue homeostasis and organ development by modulating key signaling pathways. Ciliopathies are a group of genetically heterogeneous disorders resulting from defects in cilia development and function. Patients with ciliopathic disorders exhibit a range of phenotypes that include nephronophthisis (NPHP), a progressive tubulointerstitial kidney disease that commonly results in end-stage renal disease (ESRD). In recent years, distal appendages (DAPs), which radially project from the distal end of the mother centriole, have been shown to play a vital role in primary ciliary vesicle docking and the initiation of ciliogenesis. Mutations in the genes encoding these proteins can result in either a complete loss of the primary cilium, abnormal ciliary formation, or defective ciliary signaling. DAPs deficiency in humans or mice commonly results in NPHP. In this review, we outline recent advances in our understanding of the molecular functions of DAPs and how they participate in nephronophthisis development.

scholarly journals Role of cytochrome c oxidase nuclear-encoded subunits in health and disease

2020 ◽  
pp. 947-965
Author(s):  
K Čunátová ◽  
D Pajuelo Reguera ◽  
J Houštěk ◽  
T Mráček ◽  
P Pecina
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Fine Tuning ◽  
Transport Chain ◽  
Associated Proteins ◽  
And Function ◽  
Structural Levels

Cytochrome c oxidase (COX), the terminal enzyme of mitochondrial electron transport chain, couples electron transport to oxygen with generation of proton gradient indispensable for the production of vast majority of ATP molecules in mammalian cells. The review summarizes current knowledge of COX structure and function of nuclear-encoded COX subunits, which may modulate enzyme activity according to various conditions. Moreover, some nuclear-encoded subunits posess tissue-specific and development-specific isoforms, possibly enabling fine-tuning of COX function in individual tissues. The importance of nuclear-encoded subunits is emphasized by recently discovered pathogenic mutations in patients with severe mitopathies. In addition, proteins substoichiometrically associated with COX were found to contribute to COX activity regulation and stabilization of the respiratory supercomplexes. Based on the summarized data, a model of three levels of quaternary COX structure is postulated. Individual structural levels correspond to subunits of the i) catalytic center, ii) nuclear-encoded stoichiometric subunits and iii) associated proteins, which may constitute several forms of COX with varying composition and differentially regulated function.

scholarly journals GASOMEDIATOR H2S IN THROMBOSIS AND HEMOSTASIS

2020 ◽  
Vol 13 (6) ◽  
pp. 24-29
Author(s):  
Nadiya Druzhyna ◽  
Keyword(s):  
Hydrogen Sulfide ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Blood Platelet ◽  
Cell Physiology ◽  
Biologically Relevant ◽  
And Function

This review was aimed to briefly summarize current knowledge of the biological roles of gasomediator H2S in hemostasis and cardiovascular diseases. Since the discovery that mammalian cells are enzymatically producing H2S, this molecule underwent a dramatic metamorphosis from dangerous pollutant to a biologically relevant mediator. As a gasomediator, hydrogen sulfide plays a role of signaling molecule, which is involved in a number of processes in health and disease, including pathogenesis of cardiovascular abnormalities, mainly through modulating different patterns of vasculature functions and thrombotic events. Recently, several studies have provided unequivocal evidence that H2S reduces blood platelet reactivity by inhibiting different stages of platelet activation (platelet adhesion, secretion and aggregation) and thrombus formation. Moreover, H2S changes the structure and function of fibrinogen and proteins associated with fibrinolysis. Hydrogen sulfide regulates proliferation and apoptosis of vascular smooth muscle cells, thus modulating angiogenesis and vessel function. Undoubtedly, H2S is also involved in a multitude of other physiological functions. For example, it exhibits anti-inflammatory effects by inhibiting ROS production and increasing expression of antioxidant enzymes. Some studies have demonstrated the role of hydrogen sulfide as a therapeutic agent in various diseases, including cardiovascular pathologies. Further studies are required to evaluate its importance as a regulator of cell physiology and associated cardiovascular pathological conditions such as myocardial infarction and stroke.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

Sign in / Sign up

Export Citation Format

Share Document