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 RBL1/p107 Expression Levels Are Modulated by Multiple Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5025
Author(s):  
Elisa Ventura ◽  
Carmelina Antonella Iannuzzi ◽  
Francesca Pentimalli ◽  
Antonio Giordano ◽  
Andrea Morrione
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Oncogenic Signaling ◽  
Expression Levels ◽  
Close Family Member ◽  
Calcium Calmodulin Dependent ◽  
Cycle Arrest ◽  
Significant Difference ◽  
Multiple Signaling

The members of the retinoblastoma (RB) protein family, RB1/p105, retinoblastoma-like (RBL)1/p107 and RBL2/p130 are critical modulators of the cell cycle and their dysregulation has been associated with tumor initiation and progression. The activity of RB proteins is regulated by numerous pathways including oncogenic signaling, but the molecular mechanisms of these functional interactions are not fully defined. We previously demonstrated that RBL2/p130 is a direct target of AKT and it is a key mediator of the apoptotic process induced by AKT inhibition. Here we demonstrated that RBL1/p107 levels are only minorly modulated by the AKT signaling pathway. In contrast, we discovered that RBL1/p107 levels are regulated by multiple pathways linked directly or indirectly to Ca2+-dependent signaling. Inhibition of the multifunctional calcium/calmodulin-dependent kinases (CaMKs) significantly reduced RBL1/p107 expression levels and phosphorylation, increased RBL1/p107 nuclear localization and led to cell cycle arrest in G0/G1. Targeting the Ca2+-dependent endopeptidase calpain stabilized RBL1/p107 levels and counteracted the reduction of RBL1/p107 levels associated with CaMKs inhibition. Thus, these novel observations suggest a complex regulation of RBL1/p107 expression involving different components of signaling pathways controlled by Ca2+ levels, including CaMKs and calpain, pointing out a significant difference with the mechanisms modulating the close family member RBL2/p130.

scholarly journals Targeting PML-RARαand Oncogenic Signaling Pathways by Chinese Herbal MixtureTien-HsienLiquid in Acute Promyelocytic Leukemia NB4 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Chih-Jung Yao ◽  
Chia-Ming Yang ◽  
Shuang-En Chuang ◽  
Jiann-Long Yan ◽  
Chun-Yen Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Acute Promyelocytic Leukemia ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Promyelocytic Leukemia ◽  
Gel Chromatography ◽  
Oncogenic Signaling ◽  
Nb4 Cells ◽  
Chinese Herbal ◽  
Oncogenic Signaling Pathways

Tien-HsienLiquid (THL) is a Chinese herbal mixture that has been used worldwide as complementary treatment for cancer patients in the past decade. Recently, THL has been shown to induce apoptosis in various types of solid tumor cellsin vitro. However, the underlying molecular mechanisms have not yet been well elucidated. In this study, we explored the effects of THL on acute promyelocytic leukemia (APL) NB4 cells, which could be effectively treated by some traditional Chinese remedies containing arsenic trioxide. The results showed THL could induce G2/M arrest and apoptosis in NB4 cells. Accordingly, the decrease of cyclin A and B1 were observed in THL-treated cells. The THL-induced apoptosis was accompanied with caspase-3 activation and decrease of PML-RARαfusion protein. Moreover, DNA methyltransferase 1 and oncogenic signaling pathways such as Akt/mTOR, Stat3 and ERK were also down-regulated by THL. By using ethyl acetate extraction and silica gel chromatography, an active fraction of THL named as EAS5 was isolated. At about 0.5–1% of the dose of THL, EAS5 appeared to have most of THL-induced multiple molecular targeting effects in NB4 cells. Based on the findings of these multi-targeting effects, THL might be regarding as a complementary and alternative therapeutic agent for refractory APL.

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 Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 965
Author(s):  
Sixuan Li ◽  
Hongquan Zhang ◽  
Xiaofan Wei
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Prognostic Indicators ◽  
Breast Cancer Patients ◽  
Oncogenic Signaling

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

scholarly journals SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models

2020 ◽  
Vol 15 (1) ◽  
pp. 467-492 ◽  
Author(s):  
Yemin Wang ◽  
Lien Hoang ◽  
Jennifer X. Ji ◽  
David G. Huntsman
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Wide Spectrum ◽  
Gynecologic Cancer ◽  
Tumor Development ◽  
Gynecologic Cancers ◽  
Genes Encoding ◽  
Genomic Studies ◽  
Histologic Types

The SWI/SNF (mating type SWItch/Sucrose NonFermentable) chromatin remodeling complexes interact with histones and transcription factors to modulate chromatin structure and control gene expression. These evolutionarily conserved multisubunit protein complexes are involved in regulating many biological functions, such as differentiation and cell proliferation. Genomic studies have revealed frequent mutations of genes encoding multiple subunits of the SWI/SNF complexes in a wide spectrum of cancer types, including gynecologic cancers. These SWI/SNF mutations occur at different stages of tumor development and are restricted to unique histologic types of gynecologic cancers. Thus, SWI/SNF mutations have to function in the appropriate tissue and cell context to promote gynecologic cancer initiation and progression. In this review, we summarize the current knowledge of SWI/SNF mutations in the development of gynecologic cancers to provide insights into both molecular pathogenesis and possible treatment implications for these diseases.

scholarly journals Role of Stat3 in Regulating p53 Expression and Function

2005 ◽  
Vol 25 (17) ◽  
pp. 7432-7440 ◽  
Author(s):  
Guilian Niu ◽  
Kenneth L. Wright ◽  
Yihong Ma ◽  
Gabriela M. Wright ◽  
Mei Huang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Tumor Development ◽  
P53 Gene ◽  
P53 Mutations ◽  
Oncogenic Signaling ◽  
P53 Expression ◽  
And Function ◽  
Oncogenic Signaling Pathways

ABSTRACT Loss of p53 function by mutation is common in cancer. However, most natural p53 mutations occur at a late stage in tumor development, and many clinically detectable cancers have reduced p53 expression but no p53 mutations. It remains to be fully determined what mechanisms disable p53 during malignant initiation and in cancers without mutations that directly affect p53. We show here that oncogenic signaling pathways inhibit the p53 gene transcription rate through a mechanism involving Stat3, which binds to the p53 promoter in vitro and in vivo. Site-specific mutation of a Stat3 DNA-binding site in the p53 promoter partially abrogates Stat3-induced inhibition. Stat3 activity also influences p53 response genes and affects UV-induced cell growth arrest in normal cells. Furthermore, blocking Stat3 in cancer cells up-regulates expression of p53, leading to p53-mediated tumor cell apoptosis. As a point of convergence for many oncogenic signaling pathways, Stat3 is constitutively activated at high frequency in a wide diversity of cancers and is a promising molecular target for cancer therapy. Thus, repression of p53 expression by Stat3 is likely to have an important role in development of tumors, and targeting Stat3 represents a novel therapeutic approach for p53 reactivation in many cancers lacking p53 mutations.

OnPoint: A package for online experiments in motor control and motor learning

2020 ◽  
Author(s):  
Jonathan Sanching Tsay ◽  
Alan S. Lee ◽  
Guy Avraham ◽  
Darius E. Parvin ◽  
Jeremy Ho ◽  
...  
Keyword(s):  
Motor Control ◽  
Motor Learning ◽  
Open Source Software ◽  
Research Progress ◽  
Global Pandemic ◽  
Large N ◽  
Open Source Software Package ◽  
Potential Applications ◽  
Temporal And Spatial ◽  
The One

Motor learning experiments are typically run in-person, exploiting finely calibrated setups (digitizing tablets, robotic manipulandum, full VR displays) that provide high temporal and spatial resolution. However, these experiments come at a cost, not limited to the one-time expense of purchasing equipment but also the substantial time devoted to recruiting participants and administering the experiment. Moreover, exceptional circumstances that limit in-person testing, such as a global pandemic, may halt research progress. These limitations of in-person motor learning research have motivated the design of OnPoint, an open-source software package for motor control and motor learning researchers. As with all online studies, OnPoint offers an opportunity to conduct large-N motor learning studies, with potential applications to do faster pilot testing, replicate previous findings, and conduct longitudinal studies (GitHub repository: https://github.com/alan-s-lee/OnPoint).

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells

2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Nerve Fibers ◽  
Retinal Ganglion

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

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