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Interplay between Signaling Pathways and Metabolism in Brain Tumors

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 9552

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Special Issue Editors

Prof. Dr. Christina Piperi

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Guest Editor

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: neuroinflammation; neuro-oncology; neurodegeneration; epigenetics; histone modifications; signal transduction; transcription factors
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Elias A. El-Habr

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Guest Editor

Neuroscience Paris Seine-IBPS-CNRS UMR 8246-INSERM U1130, Biology Department, Sorbonne University Team "Glial Plasticity and Neuro-Oncology", Paris, France
Interests: brain tumors; metabolism; epigenetics; signaling pathways; functional cell states; single-cell RNAseq
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The incidence of brain tumors is constantly increasing, with therapeutic approaches still remaining limited. Most malignant brain neoplasms are highly invasive, heterogeneous, neurologically destructive and resistant to therapies. One source of the therapeutic resistance of brain tumors stems from the complex interconnection of intracellular networks, such as signaling pathways and metabolism, which endows tumor cells with the ability to evade anti-cancer treatments. For instance, aberrant activation of signaling pathways enables tumor cells to resist cell death and maximize drug resistance through nutrient uptake from the microenvironment. Moreover, abnormal levels of some metabolites act as second messengers that can directly or indirectly regulate signaling pathways. Understanding the dynamics of the interplay between signaling pathways and metabolism in brain tumors is therefore expected to reveal novel therapeutic vulnerabilities and target treatments.

We are pleased to invite you to this Special Issue focusing on aspects of the interface between metabolism and signaling pathways, and their deregulation in brain tumors. This Special Issue aims to provide an up-to-date overview of signal transduction pathways and metabolic changes which contribute to the aggressive phenotypes of cancer cells and tumor progression that may serve as clinical markers to improve disease diagnosis, prognosis and therapy.

In this Special Issue, original research articles, perspectives and reviews that comprehensively address the latest discoveries in the field are invited.

We look forward to receiving your contributions.

Prof. Dr. Christina Piperi
Prof. Dr. Elias A. El-Habr
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

brain tumors
intracellular signaling pathways
metabolic pathways
signaling molecules
transcription factors
genetic factors
epigenetic markers
tumor biomarkers
clinical markers
cancer therapy

Published Papers (5 papers)

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Research

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24 pages, 5112 KiB

Open AccessArticle

MYCN Amplifications and Metabolic Rewiring in Neuroblastoma

by Marialena Pouliou, Marianna A. Koutsi, Lydia Champezou, Angeliki-Ioanna Giannopoulou, Giannis Vatsellas, Christina Piperi and Marios Agelopoulos

Cancers 2023, 15(19), 4803; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15194803 - 29 Sep 2023

Viewed by 1102

Abstract

Cancer is a disease caused by (epi)genomic and gene expression abnormalities and characterized by metabolic phenotypes that are substantially different from the normal phenotypes of the tissues of origin. Metabolic reprogramming is one of the key features of tumors, including those established in the human nervous system. In this work, we emphasize a well-known cancerous genomic alteration: the amplification of MYCN and its downstream effects in neuroblastoma phenotype evolution. Herein, we extend our previous computational biology investigations by conducting an integrative workflow applied to published genomics datasets and comprehensively assess the impact of MYCN amplification in the upregulation of metabolism-related transcription factor (TF)-encoding genes in neuroblastoma cells. The results obtained first emphasized overexpressed TFs, and subsequently those committed in metabolic cellular processes, as validated by gene ontology analyses (GOs) and literature curation. Several genes encoding for those TFs were investigated at the mechanistic and regulatory levels by conducting further omics-based computational biology assessments applied on published ChIP-seq datasets retrieved from MYCN-amplified- and MYCN-enforced-overexpression within in vivo systems of study. Hence, we approached the mechanistic interrelationship between amplified MYCN and overexpression of metabolism-related TFs in neuroblastoma and showed that many are direct targets of MYCN in an amplification-inducible fashion. These results illuminate how MYCN executes its regulatory underpinnings on metabolic processes in neuroblastoma. Full article

(This article belongs to the Special Issue Interplay between Signaling Pathways and Metabolism in Brain Tumors)

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17 pages, 1743 KiB

Open AccessArticle

MEOX2 Regulates the Growth and Survival of Glioblastoma Stem Cells by Modulating Genes of the Glycolytic Pathway and Response to Hypoxia

by Carla Proserpio, Silvia Galardi, Maria Giovanna Desimio, Alessandro Michienzi, Margherita Doria, Antonella Minutolo, Claudia Matteucci and Silvia Anna Ciafrè

Cancers 2022, 14(9), 2304; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092304 - 06 May 2022

Cited by 2 | Viewed by 1730

Abstract

The most widely accepted hypothesis for the development of glioblastoma suggests that glioblastoma stem-like cells (GSCs) are crucially involved in tumor initiation and recurrence as well as in the occurrence of chemo- and radio-resistance. Mesenchyme homeobox 2 (MEOX2) is a transcription factor overexpressed in glioblastoma, whose expression is negatively correlated with patient survival. Starting from our observation that MEOX2 expression is strongly enhanced in six GSC lines, we performed shRNA-mediated knock-down experiments in two different GSC lines and found that MEOX2 depletion resulted in the inhibition of cell growth and sphere-forming ability and an increase in apoptotic cell death. By a deep transcriptome analysis, we identified a core group of genes modulated in response to MEOX2 knock-down. Among these genes, the repressed ones are largely enriched in genes involved in the hypoxic response and glycolytic pathway, two strictly related pathways that contribute to the resistance of high-grade gliomas to therapies. An in silico study of the regulatory regions of genes differentially expressed by MEOX2 knock-down revealed that they mainly consisted of GC-rich regions enriched for Sp1 and Klf4 binding motifs, two main regulators of metabolism in glioblastoma. Our results show, for the first time, the involvement of MEOX2 in the regulation of genes of GSC metabolism, which is essential for the survival and growth of these cells. Full article

(This article belongs to the Special Issue Interplay between Signaling Pathways and Metabolism in Brain Tumors)

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Review

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18 pages, 697 KiB

Open AccessReview

Anaplastic Lymphoma Kinase (ALK) in Posterior Cranial Fossa Tumors: A Scoping Review of Diagnostic, Prognostic, and Therapeutic Perspectives

by Danai-Priskila V. Mousa, Georgios Mavrovounis, Dionysios Argyropoulos, George Stranjalis and Theodosis Kalamatianos

Cancers 2024, 16(3), 650; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16030650 - 02 Feb 2024

Viewed by 1005

Abstract

Anaplastic Lymphoma Kinase (ALK) has been implicated in several human cancers. This review aims at mapping the available literature on the involvement of ALK in non-glial tumors localized in the posterior cranial fossa and at identifying diagnostic, prognostic, and therapeutic considerations. Following the PRISMA-ScR guidelines, studies were included if they investigated ALK’s role in primary CNS, non-glial tumors located in the posterior cranial fossa. A total of 210 manuscripts were selected for full-text review and 16 finally met the inclusion criteria. The review included 55 cases of primary, intracranial neoplasms with ALK genetic alterations and/or protein expression, located in the posterior fossa, comprising of medulloblastoma, anaplastic large-cell lymphoma, histiocytosis, inflammatory myofibroblastic tumors, and intracranial myxoid mesenchymal tumors. ALK pathology was investigated via immunohistochemistry or genetic analysis. Several studies provided evidence for potential diagnostic and prognostic value for ALK assessment as well as therapeutic efficacy in its targeting. The available findings on ALK in posterior fossa tumors are limited. Nevertheless, previous findings suggest that ALK assessment is of diagnostic and prognostic value in medulloblastoma (WNT-activated). Interestingly, a substantial proportion of ALK-positive/altered CNS histiocytoses thus far identified have been localized in the posterior fossa. The therapeutic potential of ALK inhibition in histiocytosis warrants further investigation. Full article

(This article belongs to the Special Issue Interplay between Signaling Pathways and Metabolism in Brain Tumors)

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25 pages, 2083 KiB

Open AccessReview

Emerging Roles of TRIM Family Proteins in Gliomas Pathogenesis

by Angeliki-Ioanna Giannopoulou, Charalampos Xanthopoulos, Christina Piperi and Efterpi Kostareli

Cancers 2022, 14(18), 4536; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14184536 - 19 Sep 2022

Cited by 1 | Viewed by 2318

Abstract

Gliomas encompass a vast category of CNS tumors affecting both adults and children. Treatment and diagnosis are often impeded due to intratumor heterogeneity and the aggressive nature of the more malignant forms. It is therefore essential to elucidate the molecular mechanisms and explore the intracellular signaling pathways underlying tumor pathology to provide more promising diagnostic, prognostic, and therapeutic tools for gliomas. The tripartite motif-containing (TRIM) superfamily of proteins plays a key role in many physiological cellular processes, including brain development and function. Emerging evidence supports the association of TRIMs with a wide variety of cancers, exhibiting both an oncogenic as well as a tumor suppressive role depending on cancer type. In this review, we provide evidence of the pivotal role of TRIM proteins in gliomagenesis and exploit their potential as prognostic biomarkers and therapeutic targets. Full article

(This article belongs to the Special Issue Interplay between Signaling Pathways and Metabolism in Brain Tumors)

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22 pages, 2040 KiB

Open AccessReview

Crosstalk of Epigenetic and Metabolic Signaling Underpinning Glioblastoma Pathogenesis

by Mariam Markouli, Dimitrios Strepkos, Kostas A. Papavassiliou, Athanasios G. Papavassiliou and Christina Piperi

Cancers 2022, 14(11), 2655; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112655 - 27 May 2022

Cited by 6 | Viewed by 2579

Abstract

Metabolic alterations in neoplastic cells have recently gained increasing attention as a main topic of research, playing a crucial regulatory role in the development and progression of tumors. The interplay between epigenetic modifications and metabolic pathways in glioblastoma cells has emerged as a key pathogenic area with great potential for targeted therapy. Epigenetic mechanisms have been demonstrated to affect main metabolic pathways, such as glycolysis, pentose phosphate pathway, gluconeogenesis, oxidative phosphorylation, TCA cycle, lipid, and glutamine metabolism by modifying key regulatory genes. Although epigenetic modifications can primarily promote the activity of metabolic pathways, they may also exert an inhibitory role. In this way, they participate in a complex network of interactions that regulate the metabolic behavior of malignant cells, increasing their heterogeneity and plasticity. Herein, we discuss the main epigenetic mechanisms that regulate the metabolic pathways in glioblastoma cells and highlight their targeting potential against tumor progression. Full article

(This article belongs to the Special Issue Interplay between Signaling Pathways and Metabolism in Brain Tumors)

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