Signal Transduction to Transcription Factors in Health and Disease—Honorary Special Issue Commemorating the Work of Prof. Athanasios G. Papavassiliou

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3358

Special Issue Editors


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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
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Guest Editor
Weill Cornell Medical College, Hospital for Special Surgery, New York, NY, USA
Interests: autoimmunity; inflammation; rheumatic diseases; signal transduction; transcription factors; drug development

Special Issue Information

Dear Colleagues,

This year marks the 30th anniversary of the publication of Professor Athanasios G. Papavassiliou’s seminal papers on the proto-oncogene products/components of the AP-1 transcription factor, c-Jun and c-Fos (Science 258(5090):1941-4, 1992; Proc Natl Acad Sci USA 89(23):11562-5, 1992; EMBO J 14(9):2014-19, 1995; N Engl J Med 332(1):45-7, 1995), where he elucidated crucial aspects of their transcriptional activity and introduced the concept of ‘intramolecular signal transduction’.

These mechanistic papers inspired the interest of many scientists to explore the functional elements and the biological roles of transcription factors and investigate their regulation as well as their implication in a broad spectrum of human pathophysiologies.

Over the past 30 years, intensive research has unraveled the structural diversity and multifaceted action of transcription factors as key control elements of mammalian gene expression and signal transduction outcome in health and disease, establishing the field of molecular medicine. Professor Papavassiliou remained on the forefront of these efforts, and pioneered, among others, some of the functions of transcription factors AP-1, Cbfa1 (Runx2), E2F-1, NF-κB, and STAT-3, such as their involvement in cell differentiation, cell metabolism, mechanotransduction, and tumorigenesis, highlighting their potential to be used for the design of novel small-molecule selective drugs to treat a wide gamut of human maladies.

This Special Issue is focused on the role of transcription factors (and their co-factors) in various cells and tissues in health and disease. These roles include an intricate array of gene expression modulatory effects and their impact on the development and progression of endocrine, cardiovascular, respiratory, gastrointestinal, nervous, and immune system disorders and malignancies.

The Special Issue begins with a brief overview of Professor Papavassiliou’s contributions to the field, followed by original research and review articles on the molecular mechanisms underpinning the function of transcription factors in normal cell physiology and the diseased state.

Dr. Christina Piperi
Dr. George D. Kalliolias
Guest Editors

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Published Papers (3 papers)

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Editorial

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2 pages, 146 KiB  
Editorial
Integrating Signaling Pathways with Transcription Factor Networks—On the Trail of Sisyphus?
by Kostas A. Papavassiliou and Athanasios G. Papavassiliou
Biomolecules 2024, 14(8), 1015; https://doi.org/10.3390/biom14081015 - 16 Aug 2024
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Abstract
In the context of health and disease research, cells use signaling pathways that transduce stimuli from the extracellular environment to modulate intracellular gene expression via the activity of transcription factors and cofactors (coactivators and/or corepressors) [...] Full article

Research

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19 pages, 5414 KiB  
Article
Application of Graph Models to the Identification of Transcriptomic Oncometabolic Pathways in Human Hepatocellular Carcinoma
by Sergio Barace, Eva Santamaría, Stefany Infante, Sara Arcelus, Jesus De La Fuente, Enrique Goñi, Ibon Tamayo, Idoia Ochoa, Miguel Sogbe, Bruno Sangro, Mikel Hernaez, Matias A. Avila and Josepmaria Argemi
Biomolecules 2024, 14(6), 653; https://doi.org/10.3390/biom14060653 - 3 Jun 2024
Cited by 1 | Viewed by 1144
Abstract
Whole-tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly [...] Read more.
Whole-tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods. However, metabolism-related gene signatures are poorly co-expressed when applied to a biological context. Here, we apply a simple method to infer highly consistent signatures using graph-based statistics. Using the Cancer Genome Atlas Liver Hepatocellular cohort (LIHC), we describe the main metabolic clusters and their relationship with commonly used molecular classes, and with the presence of TP53 or CTNNB1 driver mutations. We find similar results in our validation cohort, the LIRI-JP cohort. We describe how previously described metabolic subtypes could not have therapeutic relevance due to their overall downregulation when compared to non-tumoral liver, and identify N-glycan, mevalonate and sphingolipid biosynthetic pathways as the hallmark of the oncogenic shift of the use of acetyl-coenzyme A in HCC metabolism. Finally, using DepMap data, we demonstrate metabolic vulnerabilities in HCC cell lines. Full article
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Review

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15 pages, 1028 KiB  
Review
Emerging Role of the Slit/Roundabout (Robo) Signaling Pathway in Glioma Pathogenesis and Potential Therapeutic Options
by Mariam Markouli, Athina Papachristou, Anastasios Politis, Efstathios Boviatsis and Christina Piperi
Biomolecules 2024, 14(10), 1231; https://doi.org/10.3390/biom14101231 - 29 Sep 2024
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Abstract
Gliomas represent the most common primary Central Nervous System (CNS) tumors, characterized by increased heterogeneity, dysregulated intracellular signaling, extremely invasive properties, and a dismal prognosis. They are generally resistant to existing therapies and only a few molecular targeting options are currently available. In [...] Read more.
Gliomas represent the most common primary Central Nervous System (CNS) tumors, characterized by increased heterogeneity, dysregulated intracellular signaling, extremely invasive properties, and a dismal prognosis. They are generally resistant to existing therapies and only a few molecular targeting options are currently available. In search of signal transduction pathways with a potential impact in glioma growth and immunotherapy, the Slit guidance ligands (Slits) and their Roundabout (Robo) family of receptors have been revealed as key regulators of tumor cells and their microenvironment. Recent evidence indicates the implication of the Slit/Robo signaling pathway in inflammation, cell migration, angiogenesis, and immune cell infiltration of gliomas, suppressing or promoting the expression of pivotal proteins, such as cell adhesion molecules, matrix metalloproteinases, interleukins, angiogenic growth factors, and immune checkpoints. Herein, we discuss recent data on the significant implication of the Slit/Robo signaling pathway in glioma pathology along with the respective targeting options, including immunotherapy, monoclonal antibody therapy, and protein expression modifiers. Full article
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