Cell Signaling

Fear can be induced either through direct experience of threat or through observation of others’ distress. This capacity for observational fear provides a survival advantage by enabling vicarious, social learning of potential danger and forms a foundation for empathy. While the anterior cingulate cortex (ACC) has long been implicated in mediating observational fear, the neuromodulatory mechanisms that distinguish it from direct fear have been unclear.

Tumor-derived exosomes (TDES) play a vital role in facilitating cancer development and dissemination through the trafficking of oncogenic nucleic acids and proteins, such as cytokines and chemokines, which remodel the tumor microenvironment (TME) to facilitate malignant traits. This process ultimately contributes to tumorigenesis, invasion, metastasis, and treatment resistance. Therefore, restricting cancer-induced communication with healthy cells by eliminating TDEs may serve as a promising approach to curb cancer progression and dissemination.

The first issue of Cell Signaling in 2025 provides an interdisciplinary overview of cellular communication, covering topics ranging from neuronal and metabolic regulation to immune evolution and regenerative processes. The studies featured in this volume collectively demonstrate how signaling pathways govern the delicate, finely tuned balance between adaptation and dysfunction, and how their manipulation continues to inspire biotechnological and therapeutic innovation.

GEMIN5 is a modular RNA-binding protein responsible for the recognition of snRNAs through its WD40 domain placed at the N-terminus. A dimerization module at the central region of the protein acts as a hub for protein-protein interaction, and a non-canonical RNA-binding domain is placed towards the C-terminus. Recent studies reported loss of function Gemin5 biallelic variants which develop cerebellar ataxia, hypotonia and neurodevelopmental delay, indicating that GEMIN5 deficiency is detrimental for survival.

Salt (sodium chloride) and A2A adenosine receptors (A2AR) have both been implicated in blood pressure regulation. While high salt consumption raises blood pressure, A2AR is a key mediator of coronary vasodilation. Although a sodium ion binding pocket has been identified in A2AR, the physiological link between salt and A2AR remains poorly investigated. Hereby, we explored how salt modulates its expression and function in vitro. 

Cell signaling represents a highly coordinated molecular dialogue that governs cellular behavior and tissue homeostasis. Among its many facets, redox signaling has emerged as a pivotal mechanism, transforming our understanding of reactive oxygen species (ROS) from mere metabolic byproducts to essential messengers [1]. Historically associated with oxidative stress and cellular damage, ROS are now recognized as regulators of physiological processes through reversible oxidation of cysteine residues in proteins.

Breast cancer remains a heterogeneous disease in which prognostic stratification, particularly within estrogen receptor (ER)-negative subtypes, remains clinically challenging. While genomic and transcriptomic profiling have advanced risk classification, protein-level regulation and subcellular localization are rarely incorporated into prognostic frameworks. NEDD8 ultimate buster 1 (NUB1) is a proteostasis-associated protein involved in degradation of ubiquitin-like modifiers and regulation of cell-cycle progression.

Low-frequency somatic mutations accumulate in normal tissues throughout life and contribute to cancer initiation, yet their detection is limited by the sensitivity of conventional sequencing methods. We describe CarcSeq, an error-corrected, targeted next-generation sequencing platform developed to quantify rare cancer driver mutations (CDMs) at variant allele frequencies as low as ~10^-4. CarcSeq integrates high-fidelity amplification, unique molecular identifiers, and single-strand consensus sequencing to accurately measure mutant frequency (MF) across a curated panel of sequences encompassing recurrent oncogene and tumor suppressor hotspots.

New efficacious and safe therapies are needed for patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. A bioinformatic approach comparing human PDAC tumors to normal pancreas identified differentially expressed G protein-coupled receptors (GPCRs). The GPCRs with higher differential expression in PDAC included the histamine H1 receptor (HRH1), which, on average, is ~20-fold higher expressed in PDAC tumors. HRH1 is readily targetable by approved H1-antihistamines.

In uveal melanoma (UM), increased M2 macrophage infiltration and high tumor pigmentation are well-established adverse prognostic features, yet their biological interplay remains underexplored. Emerging evidence indicates that these characteristics frequently coexist in genetically high-risk tumors, particularly those with monosomy 3 and BAP1 loss.

VQ motif-containing proteins represent a plant-specific class of transcriptional cofactors that integrate developmental and stress-responsive signaling pathways. Recent genome-wide characterization of the VQ gene family in the recretohalophyte L. bicolor identified LbVQ6 as a key regulator of salt gland development and salinity tolerance. 

In our recent published study entitled “Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to a Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation”, we explore the effect of a new approach for the treatment of ovarian cancer.

Snail embryos are textbook exemplars of autonomous cellular decision-making: in their spiral cleavage nearly every early cell division is asymmetric and oriented, creating a stereotyped and elaborate early pattern of fate-restricted cells (Figure 1A) reminiscent of the preformationist ‘homunculus’ fantasy. 

To maintain identity and epigenetic balance, a cell relies on robust transcriptional programs regulated both by transcription factors and by dynamic chromatin states. These states, which enable or restrict gene expression and genome function, are shaped by the incorporation of histone variants into nucleosomes and their post-translational modifications.

We have previously described the generation of Metal Organic Biohybrids (MOBs) as self-assembling structures that are formed by a combination of a biological component (amino acid), and a metal, such as copper. This MOBs synthesis process has now been distilled to be purely biochemical (a green chemistry process), or abiotic, not requiring the presence of cells. 

The recent identification of DEVIL/ROTUNDIFOLIA-like (SiDVL/RTFL) peptides from foxtail millet (Setaria italica) as negative regulators of auxin signaling has provided important insights into how small peptides orchestrate root development.

The methodology employed in this study demonstrates coherence through its integrative approach. Numerous reviews have thoroughly documented the impacts of various environmental stresses on plant physiology and morphology.