scholarly journals The Role of Epac in Cancer Progression

2020 ◽  
Vol 21 (18) ◽  
pp. 6489 ◽  
Author(s):  
Nadine Wehbe ◽  
Hasan Slika ◽  
Joelle Mesmar ◽  
Suzanne A. Nasser ◽  
Gianfranco Pintus ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Effector Protein ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Oxygen Species ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Underlying Mechanisms

Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals Protein-Protein Interaction Network Analysis and Identification of Key Players in nor-NOHA and NOHA Mediated Pathways for Treatment of Cancer through Arginase Inhibition: Insights from Systems Biology

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Systems Biology ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Key Players ◽  
Protein Protein Interaction Network

<p>L-arginine is involved in a number of biological processes in our bodies. Metabolism of L-arginine by the enzyme arginase has been found to be associated with cancer cell proliferation. Arginase inhibition has been proposed as a potential therapeutic means to inhibit this process. N-hydroxy-nor-L-Arg (nor-NOHA) and N (omega)-hydroxy-L-arginine (NOHA) has shown promise in inhibiting cancer progression through arginase inhibition. In this study, nor-NOHA and NOHA-associated genes and proteins were analyzed with several Bioinformatics and Systems Biology tools to identify the associated pathways and the key players involved so that a more comprehensive view of the molecular mechanisms including the regulatory mechanisms can be achieved and more potential targets for treatment of cancer can be discovered. Based on the analyses carried out, 3 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with nor-NOHA and NOHA associated genes. Out of the 1996 proteins in the PPI network, 4 have been identified as hub proteins- SOD, SOD1, AMD1, and NOS2. These 4 proteins have been implicated in cancer by other studies. Thus, this study provided further validation into the claim of these 4 proteins being potential targets for cancer treatment.</p>

scholarly journals Rapid metabolic and bioenergetic adaptations of astrocytes under hyperammonemia – a novel perspective on hepatic encephalopathy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marcel Zimmermann ◽  
Andreas S. Reichert
Keyword(s):  
Hepatic Encephalopathy ◽  
Molecular Mechanisms ◽  
Tca Cycle ◽  
Therapeutic Strategies ◽  
Cellular Processes ◽  
Cellular Models ◽  
The Tca Cycle ◽  
Underlying Mechanisms

Abstract Hepatic encephalopathy (HE) is a well-studied, neurological syndrome caused by liver dysfunctions. Ammonia, the major toxin during HE pathogenesis, impairs many cellular processes within astrocytes. Yet, the molecular mechanisms causing HE are not fully understood. Here we will recapitulate possible underlying mechanisms with a clear focus on studies revealing a link between altered energy metabolism and HE in cellular models and in vivo. The role of the mitochondrial glutamate dehydrogenase and its role in metabolic rewiring of the TCA cycle will be discussed. We propose an updated model of ammonia-induced toxicity that may also be exploited for therapeutic strategies in the future.

scholarly journals The Role of Omics Approaches to Characterize Molecular Mechanisms of Rare Ovarian Cancers: Recent Advances and Future Perspectives

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1481
Author(s):  
Yashwanth Subbannayya ◽  
Riccardo Di Fiore ◽  
Silvana Anna Maria Urru ◽  
Jean Calleja-Agius
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Delayed Diagnosis ◽  
Cancer Recurrence ◽  
Potential Candidate ◽  
Ovarian Cancers ◽  
Current Review ◽  
Mechanisms Of Carcinogenesis ◽  
Underlying Mechanisms

Rare ovarian cancers are ovarian cancers with an annual incidence of less than 6 cases per 100,000 women. They generally have a poor prognosis due to being delayed diagnosis and treatment. Exploration of molecular mechanisms in these cancers has been challenging due to their rarity and research efforts being fragmented across the world. Omics approaches can provide detailed molecular snapshots of the underlying mechanisms of these cancers. Omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, can identify potential candidate biomarkers for diagnosis, prognosis, and screening of rare gynecological cancers and can aid in identifying therapeutic targets. The integration of multiple omics techniques using approaches such as proteogenomics can provide a detailed understanding of the molecular mechanisms of carcinogenesis and cancer progression. Further, omics approaches can provide clues towards developing immunotherapies, cancer recurrence, and drug resistance in tumors; and form a platform for personalized medicine. The current review focuses on the application of omics approaches and integrative biology to gain a better understanding of rare ovarian cancers.

scholarly journals Adding a “Notch” to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach

2021 ◽  
Vol 9 ◽  
Author(s):  
Luisa Marracino ◽  
Francesca Fortini ◽  
Esmaa Bouhamida ◽  
Francesca Camponogara ◽  
Paolo Severi ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Molecular Mechanisms ◽  
Notch Pathway ◽  
Biological Processes ◽  
Rna Sequences ◽  
Regulate Gene Expression ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Mirnas Expression

Dysregulation of the Notch pathway is implicated in the pathophysiology of cardiovascular diseases (CVDs), but, as of today, therapies based on the re-establishing the physiological levels of Notch in the heart and vessels are not available. A possible reason is the context-dependent role of Notch in the cardiovascular system, which would require a finely tuned, cell-specific approach. MicroRNAs (miRNAs) are short functional endogenous, non-coding RNA sequences able to regulate gene expression at post-transcriptional levels influencing most, if not all, biological processes. Dysregulation of miRNAs expression is implicated in the molecular mechanisms underlying many CVDs. Notch is regulated and regulates a large number of miRNAs expressed in the cardiovascular system and, thus, targeting these miRNAs could represent an avenue to be explored to target Notch for CVDs. In this Review, we provide an overview of both established and potential, based on evidence in other pathologies, crosstalks between miRNAs and Notch in cellular processes underlying atherosclerosis, myocardial ischemia, heart failure, calcification of aortic valve, and arrhythmias. We also discuss the potential advantages, as well as the challenges, of using miRNAs for a Notch-based approach for the diagnosis and treatment of the most common CVDs.

scholarly journals The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2140
Author(s):  
Marina Andrade-Tomaz ◽  
Izadora de Souza ◽  
Clarissa Ribeiro Reily Rocha ◽  
Luciana Rodrigues Gomes
Keyword(s):  
Cell Cycle ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cell Cycle Control ◽  
Hypoxia Inducible Factor ◽  
Cellular Processes ◽  
Hypoxia Inducible Factor 1 ◽  
Chaperone Mediated Autophagy ◽  
Transformation Processes

The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes can interfere with the cell cycle, including autophagy, the catabolic pathway involved in degradation of intracellular constituents in lysosomes. According to the mechanism used to deliver cargo to the lysosome, autophagy can be classified as macroautophagy (MA), microautophagy (MI), or chaperone-mediated autophagy (CMA). Distinct from other autophagy types, CMA substrates are selectively recognized by a cytosolic chaperone, one-by-one, and then addressed for degradation in lysosomes. The function of MA in cell cycle control, and its influence in cancer progression, are already well-established. However, regulation of the cell cycle by CMA, in the context of tumorigenesis, has not been fully addressed. This review aims to present and debate the molecular mechanisms by which CMA can interfere in the cell cycle, in the context of cancer. Thus, cell cycle modulators, such as MYC, hypoxia-inducible factor-1 subunit alpha (HIF-1α), and checkpoint kinase 1 (CHK1), regulated by CMA activity will be discussed. Finally, the review will focus on how CMA dysfunction may impact the cell cycle, and as consequence promote tumorigenesis.

scholarly journals Protein-Protein Interaction Network Analysis and Identification of Key Players in nor-NOHA and NOHA Mediated Pathways for Treatment of Cancer through Arginase Inhibition: Insights from Systems Biology

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Systems Biology ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Key Players ◽  
Protein Protein Interaction Network

L-arginine is involved in a number of biological processes in our bodies. Metabolism of L-arginine by the enzyme arginase has been found to be associated with cancer cell proliferation. Arginase inhibition has been proposed as a potential therapeutic means to inhibit this process. N-hydroxy-nor-L-Arg (nor-NOHA) and N (omega)-hydroxy-L-arginine (NOHA) has shown promise in inhibiting cancer progression through arginase inhibition. In this study, nor-NOHA and NOHA-associated genes and proteins were analyzed with several Bioinformatics and Systems Biology tools to identify the associated pathways and the key players involved so that a more comprehensive view of the molecular mechanisms including the regulatory mechanisms can be achieved and more potential targets for treatment of cancer can be discovered. Based on the analyses carried out, 3 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with nor-NOHA and NOHA associated genes. Out of the 1996 proteins in the PPI network, 4 have been identified as hub proteins-SOD, SOD1, AMD1, and NOS2. These 4 proteins have been implicated in cancer by other studies. Thus, this study provided further validation into the claim of these 4 proteins being potential targets for cancer treatment.

scholarly journals Long Non-Coding RNA MEG3 in Cellular Stemness

2021 ◽  
Vol 22 (10) ◽  
pp. 5348
Author(s):  
Pei-Fang Hsieh ◽  
Cheng-Chia Yu ◽  
Pei-Ming Chu ◽  
Pei-Ling Hsieh
Keyword(s):  
Stem Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Lineage Differentiation ◽  
Non Coding Rna ◽  
Regulatory Functions ◽  
Long Non Coding Rna ◽  
Large Repertoire

Long non-coding RNAs (lncRNAs) regulate a diverse array of cellular processes at the transcriptional, post-transcriptional, translational, and post-translational levels. Accumulating evidence suggests that lncRNA MEG3 exerts a large repertoire of regulatory functions in cellular stemness. This review focuses on the molecular mechanisms by which lncRNA MEG3 functions as a signal, scaffold, guide, and decoy for multi-lineage differentiation and even cancer progression. The role of MEG3 in various types of stem cells and cancer stem cells is discussed. Here, we provide an overview of the functional versatility of lncRNA MEG3 in modulating pluripotency, differentiation, and cancer stemness.

scholarly journals Protein-Protein Interaction Network Analysis and Identification of Key Players in nor-NOHA and NOHA Mediated Pathways for Treatment of Cancer through Arginase Inhibition: Insights from Systems Biology

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Systems Biology ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Key Players ◽  
Protein Protein Interaction Network

<p>L-arginine is involved in a number of biological processes in our bodies. Metabolism of L-arginine by the enzyme arginase has been found to be associated with cancer cell proliferation. Arginase inhibition has been proposed as a potential therapeutic means to inhibit this process. N-hydroxy-nor-L-Arg (nor-NOHA) and N (omega)-hydroxy-L-arginine (NOHA) has shown promise in inhibiting cancer progression through arginase inhibition. In this study, nor-NOHA and NOHA-associated genes and proteins were analyzed with several Bioinformatics and Systems Biology tools to identify the associated pathways and the key players involved so that a more comprehensive view of the molecular mechanisms including the regulatory mechanisms can be achieved and more potential targets for treatment of cancer can be discovered. Based on the analyses carried out, 3 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with nor-NOHA and NOHA associated genes. Out of the 1996 proteins in the PPI network, 4 have been identified as hub proteins- SOD, SOD1, AMD1, and NOS2. These 4 proteins have been implicated in cancer by other studies. Thus, this study provided further validation into the claim of these 4 proteins being potential targets for cancer treatment.</p>

scholarly journals Protein-Protein Interaction Network Analysis and Identification of Key Players in nor-NOHA and NOHA Mediated Pathways for Treatment of Cancer through Arginase Inhibition: Insights from Systems Biology

2018 ◽  
Author(s):  
Ishtiaque Ahammad
Keyword(s):  
Systems Biology ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Key Players ◽  
Protein Protein Interaction Network

AbstractL-arginine is involved in a number of biological processes in our bodies. Metabolism of L-arginine by the enzyme arginase has been found to be associated with cancer cell proliferation. Arginase inhibition has been proposed as a potential therapeutic means to inhibit this process. N-hydroxy-nor-L-Arg (nor-NOHA) and N (omega)-hydroxy-L-arginine (NOHA) has shown promise in inhibiting cancer progression through arginase inhibition. In this study, nor-NOHA and NOHA-associated genes and proteins were analyzed with several Bioinformatics and Systems Biology tools to identify the associated pathways and the key players involved so that a more comprehensive view of the molecular mechanisms including the regulatory mechanisms can be achieved and more potential targets for treatment of cancer can be discovered. Based on the analyses carried out, 3 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with nor-NOHA and NOHA associated genes. Out of the 1996 proteins in the PPI network, 4 have been identified as hub proteins-SOD, SOD1, AMD1, and NOS2. These 4 proteins have been implicated in cancer by other studies. Thus, this study provided further validation into the claim of these 4 proteins being potential targets for cancer treatment.

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