Cell Signaling

Commentary Open Access

The lateralized locus coeruleus as a switch between direct and vicarious fear

Jong-Hyun Kim , Hee-sup Shin

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.

Commentary Open Access

Disrupting oncogenic dialogue: An anti-TDE vaccine to block tumor progression and metastasis

Stephene S. Meena , Geofrey F. Soko , Ray P.S. Han

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.

Editorial Open Access

Cellular conversations at the crossroads of health and disease

Anne-Sophie Armand , Patrice X. Petit

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.

Commentary Open Access

Emerging hallmarks of GEMIN5 in neurodevelopmental disease

Encarnacion Martinez-Salas, PhD , Salvador Abellan , Rosario Francisco-Velilla

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.

Original Research Open Access

Effects of salt on A2A adenosine receptors expression and function: in vitro approach and pathophysiological perspectives

Farid El Oufir , Aboubacar Sow , Claire Guiol , Marion Marlinge , Aissatou Pethwol Bah , Nathalie Kipson , Christine Criado , Marie-Charlotte Chaptal , Simon Lledo , Julia Dodivers , Julien Fromonot , Jean Ruf , Régis Guieu , Giovanna Mottola

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. 

Editorial Open Access

Current advances and future directions in cell signaling: redox communication and emerging therapeutic paradigms

Andrea Albieri-Borges

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.

Editorial Open Access

NUB1 protein localization as a prognostic modifier in ER-negative breast cancer

Ka-Liong Tan , Francesco Pezzella

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.

Commentary Open Access

Development of an error-corrected next-generation sequencing method for the quantification of hotspot cancer driver mutations

Kelly L. Harris

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.