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Signal Transduction Pathways: From Molecular Mechanisms to Therapeutic Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 1156

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Guest Editor
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Interests: endothelial cells; protein phosphatases; protein-protein interaction; cell signaling; lung diseases; angiogenesis; posttranslational modifications
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Special Issue Information

Dear Colleagues,

Signal transduction pathways are fundamental to how cells detect and respond to environmental signals, orchestrating essential biological processes such as proliferation, differentiation, metabolism, and apoptosis. These pathways are initiated by extracellular signals, such as hormones, growth factors, and cytokines, binding to specific cell surface or intracellular receptors, triggering intracellular cascades involving second messengers, kinases, phosphatases, and transcription factors. These cascades are finely regulated through feedback loops, scaffolding proteins, and post-translational modifications, ensuring signal specificity and dynamic control. Disruptions in these pathways are associated with a wide range of human diseases, including cancer, neurodegeneration, cardiovascular disorders, and immune dysfunctions. Understanding the molecular mechanisms of signal transduction is therefore critical for elucidating disease pathogenesis and identifying viable targets for therapeutic intervention. The scope of this Special Issue encompasses both the structural and functional analysis of signaling networks, as well as their integration at the system level. Moreover, targeting aberrant signaling has emerged as a powerful therapeutic strategy, leading to the development of small-molecule inhibitors, antibodies, and novel modulators. This Special Issue welcomes comprehensive reviews, impactful communications, and original research articles that enhance our understanding of signal transduction pathways in health and disease, while advancing the discovery of novel molecular mechanisms and therapeutic strategies.

Dr. Boratkó Anita
Guest Editor

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Keywords

  • signal transduction
  • molecular mechanism
  • cell signaling
  • disease pathways
  • therapeutic targets

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Published Papers (1 paper)

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Research

18 pages, 4550 KB  
Article
Quantification of Signal Transduction Pathway Activity in Pancreatic Ductal Adenocarcinoma
by Léon Raymakers, Lois A. Daamen, Martijn P. W. Intven, Jeanette H. W. Leusen, Patricia A. Olofsen, Anja van de Stolpe and Reinier A. P. Raymakers
Int. J. Mol. Sci. 2025, 26(23), 11385; https://doi.org/10.3390/ijms262311385 - 25 Nov 2025
Viewed by 877
Abstract
Patients with pancreatic ductal adenocarcinoma (PDAC) face a very poor prognosis despite advancements in therapeutic strategies. Signal transduction pathways (STPs) that show altered activity in cancer cells may provide new therapeutic targets. Here, we used simultaneous transcriptome-based activation profiling (STAP)-STP technology to identify [...] Read more.
Patients with pancreatic ductal adenocarcinoma (PDAC) face a very poor prognosis despite advancements in therapeutic strategies. Signal transduction pathways (STPs) that show altered activity in cancer cells may provide new therapeutic targets. Here, we used simultaneous transcriptome-based activation profiling (STAP)-STP technology to identify abnormal STP activity in PDAC. STAP-STP infers STP activity from messenger RNA expression of the target genes of each pathway-associated transcription factor, which is not possible with conventional bioinformatic analysis. We searched the Gene Expression Omnibus database for publicly available PDAC Affymetrix (GPL570) datasets and included six datasets: four datasets with samples from both normal pancreatic duct epithelial cells and PDAC tumor cells and two datasets with PDAC derived cell lines. The activity of the twelve most relevant STPs (androgen receptor, estrogen receptor, PI3K, MAPK, TGFβ, Notch, Hedgehog, Wnt, NFκB, STAT1/2 type I interferon, STAT1/2type II interferon and STAT3) was quantified. Increased activity of the MAPK, STAT3, Wnt, Hedgehog, Notch TGFβ, and NFκB pathways was found in at least two out of four datasets. In PDAC cell lines, MAPK, PI3K, and STAT3 STPs showed higher activity than in patient samples. Cell type deconvolution analysis showed a variable mixture of fibroblasts, immune cells, and tumor cells in the patient samples, which likely influenced the STP activity profile. This is the first time that STP activity has been quantified in PDAC. We conclude that PDAC is characterized by increased MAPK STP activity in combination with high Ki67 and increased activity of developmental pathways (Wnt, Hedgehog, Notch, TGFβ). Drugs targeting specific STPs will be evaluated in PDAC model systems to develop new therapies for PDAC. Full article
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