Journal of Cell Communication and Signaling最新文献

The Journal of Cell Communication and Signaling (JCCS) is dedicated to advancing understanding of how intracellular and extracellular signaling coordinate environmental sensing, gene regulation, and tissue homeostasis and how their dysregulation or misinterpretation contributes to disease. Reflecting on my first year as editor-in-chief, I am pleased to highlight the journal's continued progress and strategic development. Submissions, readership, and article diversity have grown steadily, driven by the commitment of authors, reviewers, editors, and publishing staff. JCCS remains selective yet inclusive in scope, emphasizing high-quality studies that illuminate signaling processes in health and disease. Ongoing initiatives to reduce decision times and enhance the expertise and global representation of our editorial and reviewer communities reinforce peer review as a rigorous collaborative enterprise. A key milestone ahead is the transition of JCCS manuscript handling to Wiley's Research Exchange (REX) platform, which integrates submission, integrity screening, and peer review within a unified system. This platform leverages artificial intelligence tools, metadata extraction, and ORCID integration to improve efficiency, transparency, and ethical oversight. Looking forward, JCCS aims to strengthen peer review, introduce special issues on emerging topics in cell communication, and foster greater international engagement to advance the field's scientific and collaborative frontiers.

MALT1, a multifunctional protease molecule, plays a pivotal role in the adaptive immunity by regulating immune cell survival, proliferation and activation through the nuclear transcription factor-κB (NF-κB) signaling pathway by scaffold and protease activities. Aberrant activation of MALT1 is implicated in the pathogenesis of hematologic malignancies, particularly diffuse large B-cell lymphoma, and select solid tumors. Emerging research studies highlight MALT1 inhibitors as promising therapeutic agents for B-cell malignancies, with several candidates demonstrating preclinical and clinical efficacy. Notably, agents such as safimaltib (JNJ-67856633) have shown manageable safety profiles and preliminary antitumor activity in early-phase trials for relapsed/refractory B-cell malignancies. However, MALT1-targeted therapy poses a dual challenge: although inhibiting oncogenic signaling and tumor cell proliferation, it also disrupts immunosuppressive Treg function, risking autoimmune toxicity by compromising the tumor microenvironment. This review systematically analyzes MALT1's oncogenic roles across cancers, clarifies inhibitor mechanisms, and evaluates translational challenges and strategic opportunities for precision oncology and combination immunotherapy.

Glucose deprivation (Glu-D) is a critical feature of the tumor microenvironment. Under such conditions, tumor cells seek alternative metabolic resources to maintain rapid growth and proliferation. Glutamine serves as a key alternative resource for cancer cells, yet the metabolic mechanisms involving its transporters in non-small cell lung cancer remain poorly understood. Lentiviral vectors for overexpression and knockdown of phosphoenolpyruvate carboxykinase 2 (PCK2), solute carrier family 38 member 2 (SLC38A2), and CEBPB were constructed. Transwell, flow cytometry, Western blotting, and dual-luciferase reporter assays were used to investigate the regulatory relationship between PCK2 and SLC38A2 under Glu-D, as well as their effects on cellular glutamine metabolism, glycolysis, and malignant cell behaviors. PCK2 and SLC38A2 were highly expressed in human adenocarcinomas tissues. PCK2 upregulated SLC38A2 expression, though this effect was indirect. Under Glu-D, knockdown of PCK2 or SLC38A2 significantly reduced cellular glutamine utilization, inhibited glycolysis, and suppressed malignant cell behaviors. Treatment with an AMP-activated protein kinase (AMPK) inhibitor or knockdown of CEBPB produced similar effects. PCK2 activated AMPK, which increased downstream SLC38A2 expression by activating the transcription factor CEBPB. PCK2 upregulates SLC38A2 expression via the AMPK-CEBPB axis, enhancing glutamine utilization to promote glycolysis and malignant behaviors in A549 cells under Glu-D.

Ángel Cortés, S., Rojas Zambrano, P.-M. and Vernot, J.-P. (2025), Favorable and poor prognosis B-cell precursor acute lymphoblastic leukemia subtypes reveal distinct leukemic cell properties when interacting with mesenchymal stem cells, differentially modifying their cell stemness and leukemia chemoresistance. J. Cell Commun. Signal, 19: e70009. https://doi.org/10.1002/ccs3.70009.

In the originally published article, the authors' names were included incorrectly. The correct names are mentioned below. The online version of this article has been corrected.

We apologize for this error.

Incorrect:

Ángel Cortés Santiago, Rojas Zambrano Paula-Manuela, Vernot Jean-Paul

Correct:

Santiago Ángel Cortés, Paula-Manuela Rojas Zambrano, Jean-Paul Vernot

Liver fibrosis is characterized by an abnormal buildup of extracellular matrix (ECM), which is primarily produced by hepatic stellate cells (HSCs). Laminin subunit gamma 2 (LAMC2) is an ECM protein whose functional role in hepatic fibrosis remains to be fully elucidated. Herein, we examine how LAMC2 contributes to liver fibrosis and explore the molecular mechanisms in both animal and cellular models. LAMC2 was knocked down in C57BL/6J mice with CCl4-induced liver fibrosis. Rescue experiments were conducted in sh-LAMC2-treated and recilisib (PI3K/Akt agonist)-treated mice. The transcription factors associated with LAMC2 in liver fibrosis were predicted and verified. Transforming growth factor (TGF)-β1-stimulated LX-2 cells (HSC line) were infected with lentiviral vectors for in vitro assays. LAMC2, which was enriched in the PI3K/Akt pathway, was increased in the liver tissues of mice treated with CCl4, and recilisib reversed LAMC2 knockdown-mediated alleviation of liver fibrosis in these mice. LAMC2 transcription in activated HSCs was caused by structural maintenance of chromosome protein 1A (SMC1A). The inhibitory effect of SMC1A knockdown on ECM accumulation and HSC activation was mitigated by LAMC2 overexpression. This study provides new insights and highlights the promising potential of the SMC1A/LAMC2/PI3K/Akt axis as a therapeutic target for liver fibrosis.

FGF23 excess is associated with morbidity and mortality, but the role of excessive circulating FGF23 concentrations as a causative factor of pathology is controversial. Here, we investigated the consequences of FGF23 excess in kidney disease. This study used three disease models: anti-glomerular basement membrane (anti-GBM) disease, Adriamycin nephropathy, and adenine-containing diets. Anti-GBM and Adriamycin mice and matched control mice received recombinant FGF23 (1 µg) or vehicle for six days (anti-GBM) or once (Adriamycin model), with dissection 24 h after the last injection. We established precision-cut kidney slices (PCKS) in adenine nephropathy for 24 h of treatment with recombinant FGF23 or vehicle. We assessed serum cytokines, biochemistry, and renal transcriptomes and histology of mice and patients with IgA nephropathy. RNA-Seq data and published transcriptomes underwent gene set enrichment, bulk ligand–receptor interaction analysis, and cell-type decomposition. Experimental anti-GBM disease caused decreased glomerular filtration rate, albuminuria, and renal tubular casts. FGF23 treatment increased phosphaturia and circulating soluble tumor necrosis factor receptor 1. The anti-GBM model showed FGF23-driven proinflammatory transcriptional signatures and Vcam1, Pdgfrb, and chemokine signaling, which were absent in FGF23-treated healthy mice. FGF23 increased renal macrophage content by transcriptome deconvolution and by immunofluorescence. In Adriamycin-induced nephropathy and in PCKS from adenine nephropathy, short-term FGF23 excess increased proinflammatory transcripts. Human data revealed associations between circulating FGF23 and renal immune cell infiltration. We found FGF23-driven renal patterns of proinflammatory gene and protein expression or leukocyte overabundance. The present data provide evidence that excess FGF23 directly drives inflammation in kidney disease and may serve as a therapeutic target.

Tuersong, T., Shataer, M., Chen, Y., Chen, G., Li, X., Lei, L., Younusi, A. and Ma, L. (2025), Extracellular vesicle-LncRNA HOTAIR modulates esophageal cancer chemoresistance and immune microenvironment via miR-375/CDH2 pathway. J. Cell Commun. Signal, 19: e70014. https://doi.org/10.1002/ccs3.70014.

In the originally published article, author Tayier Tuersong's affiliations were given incorrectly. The correct affiliations are shown below. The online version of this article has been corrected.

Incorrect:

Tayier Tuersong¹, Munire Shataer², Yan Chen¹, Gaosi Chen³, Xiaoling Li¹, Linjie Lei¹, Ayiguli Younusi¹, Liangying Ma¹

¹Department of Pharmacy, Xinjiang Key Laboratory of Neurological Diseases, Xinjiang Clinical Research Center for Nervous System Diseases, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China

²Department of Histology and Embryology, Basic Medical College of Xinjiang Medical University, Urumqi, China

³Department of Nephrology, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Center, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

Correct:

Tayier Tuersong^1,2, Munire Shataer³, Yan Chen¹, Gaosi Chen⁴, Xiaoling Li¹, Linjie Lei¹, Ayiguli Younusi¹, Liangying Ma¹

¹State Key Laboratory of Pathogenesis, Prevention and Treatment of High-Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China

²Department of Pharmacy, Xinjiang Key Laboratory of Neurological Diseases, Xinjiang Clinical Research Center for Nervous System Diseases, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China

³Department of Histology and Embryology, Basic Medical College of Xinjiang Medical University, Urumqi, China

⁴Department of Nephrology, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Center, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China

We apologize for this error.

This study aims to explore the mechanism of action of the Bromodomain-containing protein 4 (BRD4) inhibitor GNE-987 in the treatment of pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL), focusing on its effect in inhibiting T-ALL cell proliferation by activating the HLA Complex P5 (HCP5) Super-enhancer. Through bioinformatics approaches (including weighted gene co-expression network analysis and least absolute shrinkage and selection operator regression analysis), key factor BRD4 was identified from the Gene Expression Omnibus database, along with its related regulatory genes and Super-enhancer. In vitro experiments validated the regulatory effects of GNE-987 on the expression of BRD4 and HCP5, and its impact on T-ALL cell proliferation, colony formation, and apoptosis was assessed. Animal experiments further confirmed the efficacy of GNE-987 in inhibiting T-ALL progression by regulating HCP5. The results demonstrated that GNE-987 significantly enhances the activity of the HCP5 Super-enhancer and inhibits T-ALL cell proliferation while promoting apoptosis by downregulating BRD4. This study suggests that BRD4 and HCP5 are potential therapeutic targets for T-ALL, and GNE-987 provides a novel therapeutic strategy by targeting this regulatory axis, laying the foundation for precision therapy in T-ALL.

Intervertebral disc degeneration (IVDD) is a major contributor to chronic spinal disorders, yet the role of endocytosis in its pathogenesis remains incompletely understood. In this study, we systematically investigated endocytosis-related genes associated with IVDD by integrating bulk transcriptome data, single-cell RNA sequencing datasets, and Mendelian randomization (MR) analysis. Differential expression analyses identified six ERGs consistently dysregulated in IVDD, among which HLA-A and AP2M1 exhibited significant causal associations with disease risk in MR analysis and were further validated in independent datasets. Functional enrichment and gene set enrichment analyses indicated that these genes were closely involved in immune-related pathways, including natural killer cell-mediated cytotoxicity and mammalian target of rapamycin signaling. Immune infiltration analysis revealed marked alterations in macrophages, activated CD4⁺ T cells, and eosinophils in IVDD tissues, with strong correlations between immune cell proportions and the expression of HLA-A and AP2M1. In vitro experiments demonstrated that overexpression of HLA-A or AP2M1 promoted nucleus pulposus cell proliferation, suppressed apoptosis, and enhanced endocytic activity, whereas in vivo overexpression alleviated disc degeneration in a rat model. Collectively, these findings identify HLA-A and AP2M1 as potential biomarkers linking immune dysregulation and endocytic dysfunction in IVDD and provide new insights into the molecular mechanisms underlying disc degeneration.

Extracellular vesicles (EVs) derived from pluripotent stem cells have been reported to reprogram cancer cells to a more benign phenotype, due to its provision of an embryonic microenvironment. Here, we show that the effect of the EVs on the tumorigenicity of the cancer cell lines is cell type-dependent. First, we characterized the complement of transcription factors contained in EVs derived from human embryonic and induced pluripotent stem cell lines and subsequently treated MCF7, A431, MDA-MB-231, and DLD-1 cancer cell lines with the EVs derived from these pluripotent stem cell lines. For EV-treated MDA-MB-231 and DLD-1 cells, we found a decrease in the protein expression of CD44 and C24, which are accepted markers for cancer cell populations enriched with tumor-initiating cells, a result that corresponds to the previous reports. However, for EV-treated MCF7 and A431 cells, there was an increase in the protein expression of CD44 and C24 instead, with a corresponding increase in clonogenicity and resistance to a panel of anticancer drugs, when compared to non-exosome-treated cells. When subcutaneously implanted in nude mice, EV-treated MCF7 cells gave rise to tumors of larger size than untreated cells. The cell type-dependence of the effect of hPSC-derived EV treatment was postulated to be due to occurrence of an EMT for cells located at different locations along the epithelial–mesenchymal spectrum, leading to either an increase or decrease in tumorigenicity. Therefore, exposure to EVs does not always reduce the tumorigenicity of cancer cells but is cell type-dependent.