Journal of Cell Communication and Signaling最新文献

A mounting body of evidence suggests that the endoplasmic reticulum stress and the unfolded protein response are involved in the underlying mechanisms responsible for vascular diseases. Inositol-requiring protein 1α (IRE1α), the most ancient branch among the UPR-related signaling pathways, can possess both serine/threonine kinase and endoribonuclease (RNase) activity and can perform physiological and pathological functions. The IRE1α-signaling pathway plays a critical role in the pathology of various vascular diseases. In this review, we provide a general overview of the physiological function of IRE1α and its pathophysiological role in vascular diseases.

The endoplasmic reticulum (ER) is crucial for maintaining calcium balance, lipid biosynthesis, and protein folding. Disruptions in ER homeostasis, often due to the accumulation of misfolded or unfolded proteins, lead to ER stress, which plays a significant role in various diseases, especially cancer. Urological cancers, which account for high male mortality worldwide, pose a persistent challenge due to their incurability and tendency to develop drug resistance. Among the numerous dysregulated biological mechanisms, ER stress is a key factor in the progression and treatment response of these cancers. This review highlights the dual role of aberrant ER stress activation in urologic cancers, affecting both tumor growth and therapeutic outcomes. While ER stress can support tumor growth through pro-survival autophagy, it primarily inhibits cancer progression via apoptosis and pro-death autophagy. Interestingly, ER stress can paradoxically aid cancer progression through mechanisms such as exosome-mediated immune evasion. Additionally, the review examines how pharmacological interventions, particularly with phytochemicals, can stimulate ER stress-mediated tumor suppression. Key regulators, including PERK, IRE1α, and ATF6, are discussed for their roles in upregulating CHOP levels and triggering apoptosis. In conclusion, a deeper understanding of ER stress in urological cancers not only clarifies the complex interactions between cellular stress and cancer progression but also provides new opportunities for innovative therapeutic strategies.

Li, S., Li, S., Gao, Z. and Liu, Y. (2024), LncRNA HOTTIP promotes LPS-induced lung epithelial cell injury by recruiting DNMT1 to epigenetically regulate SP-C. J. Cell Commun. Signal, 18: e12020. https://doi.org/10.1002/ccs3.12020.

In the originally published article, the funding number was omitted. The correct sentence is:

The research was sponsored by the Scientific Research Project of Heilongjiang Health Commission (No. 2020-332).

We apologize for this error.

In vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), phosphatidylinositol 4,5-bisphosphate (PIP₂) acts as a substrate for phospholipase C (PLC)- and phosphoinositol 3-kinase (PI3K)-mediated signaling pathways and an unmodified ligand at ion channels and other macromolecules, which are key processes in the regulation of cell physiological and pathological phenotypes. It is envisaged that these distinct roles of PIP₂ are achieved by PIP₂-binding proteins, which act as PIP₂ buffers to produce discrete pools of PIP₂ that permits targeted release within the cell. This review discusses evidence for the expression, cell distribution, and role of myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP₂-binding protein, in cellular signaling and function of VSMCs. The review indicates the possibilities for MARCKS as a therapeutic target for vascular disease involving dysfunctional cell proliferation and migration, endothelial barrier permeability, and vascular contractility such as atherosclerosis, systemic and pulmonary hypertension, and sepsis.

Trabecular meshwork (TM) tissue has a crucial role in regulating aqueous humor circulation in the eye, thus maintaining normal intraocular pressure (IOP). TM dysfunction causes IOP elevation, which leads to glaucoma. To investigate biological changes in TM tissue in patients with glaucoma, we analyzed the mRNA expression microarray dataset, GSE27276. Gene ontology analysis indicated that redox microenvironment imbalance is among the main changes of TM tissue in patients with glaucoma. Subsequently, we induced oxidative stress in TM cells using the tert-butyl hydroperoxide (tBHP) treatment, to generate in vivo and in vitro models, and conducted mRNA sequencing to identify genes with critical roles in maintaining the redox microenvironment balance. We found that the tBHP caused TM dysfunction in vivo, characterized by aqueous humor circulation resistance, IOP elevation, and TM cell death. Further, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that ferroptosis signaling was enriched in tBHP-treated TM cells. Consistently, in vitro analyses showed that levels of reactive oxygen species, ferric ion, and malondialdehyde were increased after the tBHP treatment, indicating TM cell ferroptosis. Furthermore, inhibiting ferroptosis alleviated tBHP-induced TM cell injury. This study provides new insights suggesting that inhibition of ferroptosis has potential as a treatment for glaucoma.

The present manuscript reports on the progress made toward the official announcement of the first World Conference on Cellular Communication and Signaling. This conference is made possible by the Association for research on biosignaling and communication initiative, which was originally launched in 2020 and revitalized during the 12th International Workshop on the Cell Communication Network family of genes in Oslo (June 20–23, 2024). The aim of this conference is to facilitate interactions among the members of societies interested in all aspects of research on Biosignaling and Communication. It is intended to provide a platform for collaborative efforts aimed at unraveling and understanding the functioning of biological pathways in both normal and pathological conditions.

The 12th international workshop on the CCN family of genes took place at the Scandic Holmenkollen Park Hotel in Oslo, Norway from June 20–23, 2024. In 2024, it was the second time, following the Nice meeting in 2022, that the scientific topics were expanded to include additional cellular signaling and communication pathways of interest to the CCN Society members, as suggested by Bernard Perbal in 2019. The 12th international CCN workshop, organized by Håvard Attramadal and Vivi T. Monsen, along with co-organizers Bernard and Annick Perbal, was given the subtitle “Cell-matrix Communication and Functions in Health and Disease” to encompass the broader scope of this meeting. The five scientific sessions covered various topics: Extracellular Matrix Proteins in Cell Communication and Signaling (Chaired by Brahim Chaqour and Vivi T. Monsen), Vascular Development and Pathophysiology (Chaired by Lester F. Lau and Håvard Attramadal), Mechanisms of Diseases (Chaired by George Bou-Gharios and Satoshi Kubota), Tissue Development and Homeostasis (Chaired by Blandine Poulet and Bernard Perbal), and Mechanisms of Disease: Cancer and the Matrix (Chaired by Stephen M. Twigg and Raymond B. Birge). The 2024 ICCNS Award was presented to Katia Scotlandi during the last session (Chaired by Bernard Perbal) before Håvard Attramadal presented the conclusion of the workshop.

Ewing sarcoma (EwS), a highly aggressive malignancy affecting children and young adults, is primarily driven by a distinctive oncogenic fusion, the EWSR1-ETS, whose activity is a key source of epigenetic and clinical heterogeneity. CD99 is constantly present in EwS cells, known to modulate the EwS genetic profile and tumor malignancy. However, the relevance of CD99 alone, or in association with EWSR1-ETS chimeras, is poorly understood. We explored the dynamic relationship between CD99 and EWS::FLI1, the main fusion observed in EwS, by means of model systems with inducible expression of either molecule. The transcriptomic dynamics of cells with or without expression of EWS::FLI1 or CD99 were analyzed and correlated with tumor cell growth. The CD99-associated EwS gene profile was found to have commonalities with the profile induced by EWS::FLI1, but also peculiar differences. Both EWS::FLI1 and CD99 are regulated targets of the DREAM complex, but the CD99 expression specifically impacted genes that are the targets of FOXM1 and are involved in the setting of the G2/M phase of the cell cycle. Most CD99-regulated FOXM1-targeted genes were found to correlate with bad prognosis in two public clinical datasets (R2 platform), further supporting the clinical relevance of CD99-mediated regulation of EwS gene expression.

Cellular communication network factor 2 (CCN2) is a matricellular protein that plays important roles in connective tissue. CCN2 is also expressed in the nervous system; however, its role is still unclear. To explore CCN2 function in the brain, we generated forebrain-specific Ccn2 knockout (FbCcn2 KO) mice. In this study, we examined the behavioral phenotypes of FbCcn2KO mice. Male mice lacking CCN2 in the forebrain exhibited normal locomotion, sensorimotor gating, and social behaviors but signs of anxiety and elevated reactive aggression. We checked the c-fos expression in aggression-related brain regions following the resident-intruder task (RIT), an aggression test. RIT-induced c-fos levels in the medial amygdala (MeA) were higher in FbCcn2^−/− mice as compared to controls. However, in the prefrontal cortex, RIT-induced c-fos levels in FbCcn2^−/− mice were lower than controls. Our results suggested in male mice lacking CCN2 in the olfaction-related regions, olfactory social cues elicit greater signals in the MeA, resulting in greater reactive aggression in the RIT. Further, lacking CCN2 in the prefrontal cortex, the major area related to inhibitory control and emotion regulation, may lead to signs of anxiety and the failure to suppress aggressive behaviors. Our model is useful in elaborating the mechanism underlying reactive aggression and therapeutic strategies.