scholarly journals Molecular mechanisms of cross-talk between growth factors and nuclear receptor signaling

2003 ◽  
Vol 75 (11-12) ◽  
pp. 1743-1756 ◽  
Author(s):  
D. Picard
Keyword(s):  
Growth Factors ◽  
Signaling Pathways ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Steroid Receptors ◽  
Reciprocal Relationship ◽  
Signaling Crosstalk ◽  
Intracellular Signals ◽  
Wide Range ◽  
The One

Signaling pathways can be linear, but more complex patterns are common. Growth factors and many other extracellular signals cannot directly enter cells and transduce their information via membrane-bound receptors. In contrast, steroid receptors are members of the nuclear receptor superfamily and await their cognate hormones inside the cells. These two types of signaling pathways are extensively intertwined and crosstalk at many different levels. A wide range of extra- and intracellular signals, including a variety of growth factors, can activate the transcriptional activity of steroid receptors in the absence of their cognate hormones. Conversely, steroid receptors lead a double life. By coupling to signaling molecules that mediate signal transduction of extracellular factors, they can elicit very rapid nongenomic responses. The signaling pathways of steroid-independent activation of steroid receptors, on the one hand, and of nongenomic signaling by steroid receptors, on the other, display a remarkable reciprocal relationship suggesting that these two modes of signaling crosstalk may be two faces of the same coin.

scholarly journals Signaling pathways have an inherent need for noise to acquire information

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Eugenio Azpeitia ◽  
Eugenio P. Balanzario ◽  
Andreas Wagner
Keyword(s):  
Signaling Pathways ◽  
Information Acquisition ◽  
Cellular Level ◽  
Kinetic Properties ◽  
Positive Role ◽  
Binding Interactions ◽  
Reversible Binding ◽  
Wide Range ◽  
The One ◽  
Parameter Values

Abstract Background All living systems acquire information about their environment. At the cellular level, they do so through signaling pathways. Such pathways rely on reversible binding interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. These interactions are inherently stochastic and thus noisy. On the one hand, noise can cause a signaling pathway to produce the same response for different stimuli, which reduces the amount of information a pathway acquires. On the other hand, in processes such as stochastic resonance, noise can improve the detection of weak stimuli and thus the acquisition of information. It is not clear whether the kinetic parameters that determine a pathway’s operation cause noise to reduce or increase the acquisition of information. Results We analyze how the kinetic properties of the reversible binding interactions used by signaling pathways affect the relationship between noise, the response to a signal, and information acquisition. Our results show that, under a wide range of biologically sensible parameter values, a noisy dynamic of reversible binding interactions is necessary to produce distinct responses to different stimuli. As a consequence, noise is indispensable for the acquisition of information in signaling pathways. Conclusions Our observations go beyond previous work by showing that noise plays a positive role in signaling pathways, demonstrating that noise is essential when such pathways acquire information.

scholarly journals Bone remodeling stages under physiological conditions and glucocorticoid in excess: Focus on cellular and molecular mechanisms

2021 ◽  
Vol 12 (2) ◽  
pp. 212-227
Author(s):  
V. V. Povoroznyuk ◽  
N. V. Dedukh ◽  
M. A. Bystrytska ◽  
V. S. Shapovalov
Keyword(s):  
Growth Factors ◽  
Bone Resorption ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Signaling Molecules ◽  
Physiological Conditions ◽  
Bone Cell Differentiation ◽  
Repressive Effect

This review provides a rationale for the cellular and molecular mechanisms of bone remodeling stages under physiological conditions and glucocorticoids (GCs) in excess. Remodeling is a synchronous process involving bone resorption and formation, proceeding through stages of: (1) resting bone, (2) activation, (3) bone resorption, (4) reversal, (5) formation, (6) termination. Bone remodeling is strictly controlled by local and systemic regulatory signaling molecules. This review presents current data on the interaction of osteoclasts, osteoblasts and osteocytes in bone remodeling and defines the role of osteoprogenitor cells located above the resorption area in the form of canopies and populating resorption cavities. The signaling pathways of proliferation, differentiation, viability, and cell death during remodeling are presented. The study of signaling pathways is critical to understanding bone remodeling under normal and pathological conditions. The main signaling pathways that control bone resorption and formation are RANK / RANKL / OPG; M-CSF – c-FMS; canonical and non-canonical signaling pathways Wnt; Notch; MARK; TGFβ / SMAD; ephrinB1/ephrinB2 – EphB4, TNFα – TNFβ, and Bim – Bax/Bak. Cytokines, growth factors, prostaglandins, parathyroid hormone, vitamin D, calcitonin, and estrogens also act as regulators of bone remodeling. The role of non-encoding microRNAs and long RNAs in the process of bone cell differentiation has been established. MicroRNAs affect many target genes, have both a repressive effect on bone formation and activate osteoblast differentiation in different ways. Excess of glucocorticoids negatively affects all stages of bone remodeling, disrupts molecular signaling, induces apoptosis of osteocytes and osteoblasts in different ways, and increases the life cycle of osteoclasts. Glucocorticoids disrupt the reversal stage, which is critical for the subsequent stages of remodeling. Negative effects of GCs on signaling molecules of the canonical Wingless (WNT)/β-catenin pathway and other signaling pathways impair osteoblastogenesis. Under the influence of excess glucocorticoids biosynthesis of biologically active growth factors is reduced, which leads to a decrease in the expression by osteoblasts of molecules that form the osteoid. Glucocorticoids stimulate the expression of mineralization inhibitor proteins, osteoid mineralization is delayed, which is accompanied by increased local matrix demineralization. Although many signaling pathways involved in bone resorption and formation have been discovered and described, the temporal and spatial mechanisms of their sequential turn-on and turn-off in cell proliferation and differentiation require additional research.

scholarly journals STAT3, a Hub Protein of Cellular Signaling Pathways, Is Triggered by β-Hexaclorocyclohexane

2018 ◽  
Vol 19 (7) ◽  
pp. 2108 ◽  
Author(s):  
Elisabetta Rubini ◽  
Fabio Altieri ◽  
Silvia Chichiarelli ◽  
Flavia Giamogante ◽  
Stefania Carissimi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Signaling ◽  
Environmental Pollutants ◽  
Altered Expression ◽  
Exposed Population ◽  
Wide Range ◽  
Hepg2 Cell Lines

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 μM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect.

scholarly journals Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

2020 ◽  
Author(s):  
Seyyed Reza Mousavi ◽  
Nima Hemmat ◽  
Hossein Bannazadeh Baghi ◽  
Afshin Derakhshani ◽  
Stefania Tommasi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Bioinformatic Analysis ◽  
Aberrant Expression ◽  
Recurrent Cervical Cancer ◽  
Response To Chemotherapy ◽  
Wide Range ◽  
Non Coding Rnas

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

scholarly journals Tiny dancers

2002 ◽  
Vol 158 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Susan S. Smyth ◽  
Cam Patterson
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Surface Receptors

A vital step in growth factor–driven angiogenesis is the coordinated engagement of endothelial integrins with the extracellular matrix. The molecular mechanisms that partner growth factors and integrins are being elucidated, revealing an intricate interaction of surface receptors and their signaling pathways.

The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting

2021 ◽  
Vol 61 (1) ◽  
pp. 541-563 ◽  
Author(s):  
Martine J. Smit ◽  
Géraldine Schlecht-Louf ◽  
Maria Neves ◽  
Jelle van den Bor ◽  
Petronila Penela ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cancer Therapies ◽  
Signaling Crosstalk ◽  
Wide Range ◽  
Elevated Expression

Elevated expression of the chemokine receptors CXCR4 and ACKR3 and of their cognate ligand CXCL12 is detected in a wide range of tumors and the tumor microenvironment (TME). Yet, the molecular mechanisms by which the CXCL12/CXCR4/ACKR3 axis contributes to the pathogenesis are complex and not fully understood. To dissect the role of this axis in cancer, we discuss its ability to impinge on canonical and less conventional signaling networks in different cancer cell types; its bidirectional crosstalk, notably with receptor tyrosine kinase (RTK) and other factors present in the TME; and the infiltration of immune cells that supporttumor progression. We discuss current and emerging avenues that target the CXCL12/CXCR4/ACKR3 axis. Coordinately targeting both RTKs and CXCR4/ACKR3 and/or CXCL12 is an attractive approach to consider in multitargeted cancer therapies. In addition, inhibiting infiltrating immune cells or reactivating the immune system along with modulating the CXCL12/CXCR4/ACKR3 axis in the TME has therapeutic promise.

scholarly journals The positive role of noise for information acquisition in biological signaling pathways

2019 ◽  
Author(s):  
Eugenio Azpeitia ◽  
Andreas Wagner
Keyword(s):  
Signaling Pathways ◽  
Molecular Interactions ◽  
Information Acquisition ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Living Systems ◽  
Biological Information ◽  
Necessary Condition ◽  
Positive Role ◽  
Wide Range

AbstractAll living systems acquire information about their environment. At the cellular level, they do so through signaling pathways, which rely on interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. Such interactions are inherently stochastic and thus noisy. In classical information theory, a noisy communication channel degrades the amount of transmissible information relative to a noise-free channel. For this reason, one would expect that the kinetic parameters that determine a pathway’s operation minimize noise. We show that this is not the case under a wide range of biologically sensible parameter values. Specifically, we perform computational simulations of simple signaling systems, which show that a noisy molecular interaction dynamics is a necessary condition for information acquisition. Moreover, we show that optimal information acquisition, where a system reacts most sensitively to changes in the environment, can be obtained close to the maximal attainable level of noise in the system. Our work highlights the positive role that noise can have in biological information processing.Author summaryThe acquisition of information is fundamental for living systems, because the decisions they take based on such information directly affect survival and reproduction. The molecular mechanisms used by cells to acquire information are signaling pathways. The molecular interactions of signaling pathways, such as the binding of a signal to a receptor, are by nature noisy. This is important, because noise disrupts information. Hence, to maximize the acquisition of information, signaling pathways should minimize the noise of their molecular interactions. Here we show that a noisy dynamic of the molecular interactions can improve the acquisition of information, and that the maximal capacity to acquire information can be obtained with a close-to-maximal level of noise in a signaling pathway. Thus, contrary to expectations, noise can improve the acquisition of information in living systems.

scholarly journals Interplay between Epigenetics and Cellular Metabolism in Colorectal Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1406
Author(s):  
Xiaolin Zhang ◽  
Zhen Dong ◽  
Hongjuan Cui
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cellular Metabolism ◽  
Metabolic Enzymes ◽  
Oncogenic Signaling ◽  
Genes Encoding ◽  
Potential Applications ◽  
The One ◽  
Epigenetic Processes

Cellular metabolism alterations have been recognized as one of the most predominant hallmarks of colorectal cancers (CRCs). It is precisely regulated by many oncogenic signaling pathways in all kinds of regulatory levels, including transcriptional, post-transcriptional, translational and post-translational levels. Among these regulatory factors, epigenetics play an essential role in the modulation of cellular metabolism. On the one hand, epigenetics can regulate cellular metabolism via directly controlling the transcription of genes encoding metabolic enzymes of transporters. On the other hand, epigenetics can regulate major transcriptional factors and signaling pathways that control the transcription of genes encoding metabolic enzymes or transporters, or affecting the translation, activation, stabilization, or translocation of metabolic enzymes or transporters. Interestingly, epigenetics can also be controlled by cellular metabolism. Metabolites not only directly influence epigenetic processes, but also affect the activity of epigenetic enzymes. Actually, both cellular metabolism pathways and epigenetic processes are controlled by enzymes. They are highly intertwined and are essential for oncogenesis and tumor development of CRCs. Therefore, they are potential therapeutic targets for the treatment of CRCs. In recent years, both epigenetic and metabolism inhibitors are studied for clinical use to treat CRCs. In this review, we depict the interplay between epigenetics and cellular metabolism in CRCs and summarize the underlying molecular mechanisms and their potential applications for clinical therapy.

scholarly journals Signaling Pathways That Control Muscle Mass

2020 ◽  
Vol 21 (13) ◽  
pp. 4759 ◽  
Author(s):  
Anna Vainshtein ◽  
Marco Sandri
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Control Muscle ◽  
Health And Wellbeing ◽  
Multiple Protein ◽  
Wide Range ◽  
Whole Body Metabolism

The loss of skeletal muscle mass under a wide range of acute and chronic maladies is associated with poor prognosis, reduced quality of life, and increased mortality. Decades of research indicate the importance of skeletal muscle for whole body metabolism, glucose homeostasis, as well as overall health and wellbeing. This tissue’s remarkable ability to rapidly and effectively adapt to changing environmental cues is a double-edged sword. Physiological adaptations that are beneficial throughout life become maladaptive during atrophic conditions. The atrophic program can be activated by mechanical, oxidative, and energetic distress, and is influenced by the availability of nutrients, growth factors, and cytokines. Largely governed by a transcription-dependent mechanism, this program impinges on multiple protein networks including various organelles as well as biosynthetic and quality control systems. Although modulating muscle function to prevent and treat disease is an enticing concept that has intrigued research teams for decades, a lack of thorough understanding of the molecular mechanisms and signaling pathways that control muscle mass, in addition to poor transferability of findings from rodents to humans, has obstructed efforts to develop effective treatments. Here, we review the progress made in unraveling the molecular mechanisms responsible for the regulation of muscle mass, as this continues to be an intensive area of research.

scholarly journals The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

2002 ◽  
Vol 2 ◽  
pp. 892-925 ◽  
Author(s):  
Aaron N. Johnson ◽  
Stuart J. Newfeld
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Transforming Growth Factor Β ◽  
Suppressor Activity ◽  
Wide Range ◽  
Tumor Suppressor Activity ◽  
Multicellular Organisms

Intercellular communication is a critical process for all multicellular organisms, and communication among cells is required for proper embryonic development and adult physiology. Members of the Transforming Growth Factor-β (TGF-β) family of secreted proteins communicate information between cells via a complex signaling pathway, and family members are capable of inducing a wide range of cellular responses. The purpose of this review is to provide the reader with a broad introduction to our current understanding of three aspects of the TGF-β family. These are the molecular mechanisms utilized by TGF-β signaling pathways, the developmental roles played by TGF-β family members in a variety of species, and the growing list of cancers in which various TGF-β signaling pathways display tumor suppressor activity.

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