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 MOB: Pivotal Conserved Proteins in Cytokinesis, Cell Architecture and Tissue Homeostasis

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 413
Author(s):  
Inês L. S. Delgado ◽  
Bruno Carmona ◽  
Sofia Nolasco ◽  
Dulce Santos ◽  
Alexandre Leitão ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Current Knowledge ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Cell Architecture ◽  
Septation Initiation Network ◽  
Control Organ ◽  
Multicellular Organisms

The MOB family proteins are constituted by highly conserved eukaryote kinase signal adaptors that are often essential both for cell and organism survival. Historically, MOB family proteins have been described as kinase activators participating in Hippo and Mitotic Exit Network/ Septation Initiation Network (MEN/SIN) signaling pathways that have central roles in regulating cytokinesis, cell polarity, cell proliferation and cell fate to control organ growth and regeneration. In metazoans, MOB proteins act as central signal adaptors of the core kinase module MST1/2, LATS1/2, and NDR1/2 kinases that phosphorylate the YAP/TAZ transcriptional co-activators, effectors of the Hippo signaling pathway. More recently, MOBs have been shown to also have non-kinase partners and to be involved in cilia biology, indicating that its activity and regulation is more diverse than expected. In this review, we explore the possible ancestral role of MEN/SIN pathways on the built-in nature of a more complex and functionally expanded Hippo pathway, by focusing on the most conserved components of these pathways, the MOB proteins. We discuss the current knowledge of MOBs-regulated signaling, with emphasis on its evolutionary history and role in morphogenesis, cytokinesis, and cell polarity from unicellular to multicellular organisms.

scholarly journals RASSF1A-Mediated Suppression of Estrogen Receptor Alpha (ERα)-Driven Breast Cancer Cell Growth Depends on the Hippo-Kinases LATS1 and 2

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2868
Author(s):  
Sven Roßwag ◽  
Jonathan P. Sleeman ◽  
Sonja Thaler
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Suppressor ◽  
Estrogen Receptor Alpha ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Breast Cancers ◽  
Receptor Alpha ◽  
And Function

Around 70% of breast cancers express the estrogen receptor alpha (ERα). This receptor is of central importance for breast cancer development and estrogen-dependent tumor growth. However, the molecular mechanisms that are responsible for the control of ERα expression and function in the context of breast carcinogenesis are complex and not fully understood. In previous work, we have demonstrated that the tumor suppressor RASSF1A suppresses estrogen-dependent growth of breast cancer cells through a complex network that keeps ERα expression and function under control. We observed that RASSF1A mediates the suppression of ERα expression through modulation of the Hippo effector Yes-associated protein 1 (YAP1) activity. Here we report that RASSF1A-mediated alteration of YAP1 depends on the Hippo-kinases LATS1 and LATS2. Based on these results, we conclude that inactivation of RASSF1A causes changes in the function of the Hippo signaling pathway and altered activation of YAP1, and as a consequence, increased expression and function of ERα. Thus, the inactivation of RASSF1A might constitute a fundamental event that supports the initiation of ERα-dependent breast cancer. Furthermore, our results support the notion that the Hippo pathway is important for the suppression of luminal breast cancers, and that the tumor-suppressor function of RASSF1A depends on LATS1 and LATS2.

scholarly journals NDR1 functions as tumor suppressor in glioblastoma by phosphoralation of YAP

2021 ◽  
Author(s):  
Bin Chen ◽  
Bin Liu ◽  
Tao Yu ◽  
Yunfeng Han ◽  
Chao Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Tumor Suppressor ◽  
Hippo Pathway ◽  
Tumor Model ◽  
Hippo Signaling ◽  
Lower Survival Rate ◽  
Normal Tissues ◽  
Cycle Arrest

Abstract Purpose: The NDR1(Nuclear Dbf2-related) kinase is a member of the NDR/LATS family which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating YAP remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. The purpose of this study was to investigate the role of NDR1-YAP pathway in GBM. Materials and Methods: Bioinformation analysis and immunohistochemistry was performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing cck-8, clone formation, immunofluorescence and flow cytometry respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-ip and immunofluorescence. Results: Bioinformation analysis and immunohistochemistry of our petients’ tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to lower survival rate. NDR1 could markedly reduce the proliferation, colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-OE group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phophoralate YAP at S127 site. Meanwhile, NDR1 could mediate apopptosis process. Conclusion: In summary, our findings pointed out that NDR1 functions as a tumor suppressor in GBM. NDR1 was identified as a novel regulator of YAP, which give us a in depth comprehension in Hippo signaling pathway.

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.

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

scholarly journals Antioxidant and Signaling Role of Plastid-Derived Isoprenoid Quinones and Chromanols

2021 ◽  
Vol 22 (6) ◽  
pp. 2950
Author(s):  
Beatrycze Nowicka ◽  
Agnieszka Trela-Makowej ◽  
Dariusz Latowski ◽  
Kazimierz Strzalka ◽  
Renata Szymańska
Keyword(s):  
Current Knowledge ◽  
Stress Factors ◽  
Oxygenic Photosynthesis ◽  
Ros Generation ◽  
Main Site ◽  
Storage Lipids ◽  
Abiotic Stress Factors ◽  
Cell Components ◽  
And Function

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

scholarly journals The Hippo Pathway: A Master Regulatory Network Important in Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1416
Author(s):  
Qiuping Liu ◽  
Xiaomeng Liu ◽  
Guanbin Song
Keyword(s):  
Metabolic Regulation ◽  
Human Cancer ◽  
Hippo Pathway ◽  
Tumor Development ◽  
Biological Significance ◽  
Cancer Development ◽  
Hippo Signaling ◽  
Complex Regulation ◽  
And Function ◽  
The Hippo Pathway

The Hippo pathway is pervasively activated and has been well recognized to play critical roles in human cancer. The deregulation of Hippo signaling involved in cancer development, progression, and resistance to cancer treatment have been confirmed in several human cancers. Its biological significance and deregulation in cancer have drawn increasing interest in the past few years. A fundamental understanding of the complexity of the Hippo pathway in cancer is crucial for improving future clinical interventions and therapy for cancers. In this review, we try to clarify the complex regulation and function of the Hippo signaling network in cancer development, including its role in signal transduction, metabolic regulation, and tumor development, as well as tumor therapies targeting the Hippo pathway.

scholarly journals Non-Coding RNA in Pancreas and β-Cell Development

2018 ◽  
Vol 4 (4) ◽  
pp. 41 ◽  
Author(s):  
Wilson K. M. Wong ◽  
Anja E. Sørensen ◽  
Mugdha V. Joglekar ◽  
Anand A. Hardikar ◽  
Louise T. Dalgaard
Keyword(s):  
Cell Function ◽  
Islet Cells ◽  
Current Knowledge ◽  
Cell Development ◽  
Pancreas Development ◽  
Β Cell ◽  
Neighboring Gene ◽  
Non Coding Rnas ◽  
And Function

In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

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