http://www.cell-stress.com The Journal of the European Research Institute for Integrated Cellular Pathology Mon, 09 Mar 2026 15:04:15 +0000 eng hourly 60 https://wordpress.org/?v=6.3.8 http://www.cell-stress.com/researcharticles/2026a-ebadollahibaruq-cell-stress/ Mon, 09 Mar 2026 15:04:15 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9745
Shima Ebadollahibaruq, Lingbin Meng and Feng Hong

Canopy homolog protein 2 (CNPY2), an endoplasmic reticulum (ER) luminal protein exhibits broad tissue distribution and regulates cellular homeostasis, including unfolded protein responses (UPR), mitochondrial dynamics, oxidative stress, and apoptosis. Beyond its role in cancer progression through pathways such as NF-κB, AKT/GSK3β, PI3K/Akt/mTOR and HIF-1α, promoting epithelial-mesenchymal transition (EMT), tumor survival and metastasis, CNPY2 is also critical in non-cancer conditions. In neurodegenerative disorders including Parkinson’s and Huntington’s, it exerts neuroprotective role by reducing oxidative stress and mitochondrial dysfunction. In cardiovascular tissues, CNPY2 leads to hypoxia-driven angiogenesis, tissue repair, and ischemia-reperfusion protection. Moreover, recent meta-analyses have linked CNPY2 downregulation with Keratoconus pathogenesis, further highlighting its tissue- specific roles. Hence, this review meticulously dissects CNPY2’s structural characteristics, expression patterns, and biological functions across cancer, cardiovascular disease, inflammation and neurological disorders, emphasizing its role on tumor initiation, microenvironmental stress, and chemoresistance, and evaluating its potential as a therapeutic target. ]]> http://www.cell-stress.com/researcharticles/2026a-carmona-gutierrez-cell-stress/ Fri, 30 Jan 2026 21:12:21 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9740
Didac Carmona-Gutierrez, Maria A. Bauer, Katharina Kainz¸ Martin N. Odabas and Frank Madeo

Fungal infections pose a significant global health threat with rising morbidity and mortality rates. However, the repertoire of effective antifungal drugs remains narrow, a challenge that is further exacerbated by the increasing emergence of (multi)drug-resistant strains. This underscores the urgent need for novel therapeutic strategies. Among them, antifungal peptides (AFPs) have emerged as a promising alternative. AFPs are small, naturally occurring peptides produced by a wide range of organisms, including plants, animals, fungi, and bacteria, as part of their innate immune defense. In addition, synthetic and semisynthetic variants have also been engineered. We here underscore the potential of AFPs as viable candidates for the development of next-generation antifungal therapies. In particular, we advocate their multimodal advantage that spans beyond standalone activity, including their synergistic and immune-regulatory potential. ]]> http://www.cell-stress.com/researcharticles/2026a-shen-cell-stress/ Mon, 26 Jan 2026 20:21:34 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9731
Zhe Shen, Hui Pan, Xiaolian Deng, Oliver Kepp, Isabelle Martins, and Guido Kroemer

Cushing syndrome (CS) is caused by an increase in endogenous or exogenous glucocorticoids, leading to major alterations in body composition, including visceral obesity, sarcopenia, osteoporosis, type 2 diabetes, and dyslipidemia. Cardiovascular complications resulting from CS are often lethal. We previously demonstrated that CS induced by oral corticosterone (CORT) supplementation in mice can be prevented by inhibition of the peptide hormone acyl-CoA binding protein (ACBP), encoded by the gene diazepam binding inhibitor (DBI). Here, we investigated whether ACBP/DBI inhibition could be used to treat, rather than prevent, CS. To this end, we initiated treatment with anti-ACBP/DBI monoclonal antibodies (mAbs) in mice three weeks after the start of CORT supplementation, when hyperphagia and body weight gain were already established. Two anti-ACBP/DBI mAbs, 7G4a (specific for mouse ACBP/DBI only) and 82 (which recognizes both mouse and human ACBP/DBI), were able to normalize food intake and halt weight gain in mice under continuous CORT treatment. In addition, both mAbs attenuated CORT-induced sarcopenia, adiposity in inguinal, perigonadal, and visceral fat depots, and fully restored metabolic parameters, including insulinemia, free fatty acids, triglycerides, and liver transaminases. In conclusion, neutralization of ACBP/DBI may serve as an effective therapeutic strategy for the treatment of established CS. ]]> http://www.cell-stress.com/researcharticles/2025a-adams-cell-stress/ Thu, 13 Nov 2025 09:01:47 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9707
Brittney Adams, Stanislaw Walkowiak and Mohammed K Hankir

Removing certain essential amino acids from the diet is known to promote weight loss in rodents via effects on food intake and energy expenditure. Two complementary articles by Varghese et al [Nature 643(8072)] and Lee et al [Nature Metabolism 7(6)] now show that cysteine depletion through combined dietary and genetic means in mice evokes a unique stress response in the liver to amplify these metabolic outcomes and offer a potentially new treatment option for obesity. ]]> http://www.cell-stress.com/researcharticles/2025a-jungk-cell-stress/ Tue, 28 Oct 2025 10:33:19 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9693
Philipp Jungk and Maik Kschischo

Replication stress (RS) is a major driver of genomic instability and cancer development through impaired DNA replication that can lead to chromo-somal instability (CIN). Although RS is mechanistically linked to CIN, its relationship with cellular proliferation is complex. Depending on the con-text, RS can either promote or suppress cell growth. Existing RS gene expression signatures overlook this complexity, relying on the overex-pression of oncogenes such as MYC, which introduces a proliferation bias. To disentangle genuine RS from confounding cell cycle and prolifer-ation transcriptional profiles, we developed and validated a novel gene expression signature that accurately predicts RS independently of onco-gene activity. This tumorigenic RS signature (TRSS) captures RS-related transcriptional changes across diverse cellular contexts, enabling a more robust and proliferation-independent measure of RS in both experimental and clinical samples. Applying our signature to patient data, we discov-ered a link between RS and the non-homologous end-joining (NHEJ) DNA repair pathway. Specifically, we observed that MSH2 and MSH6 – core components of mismatch repair – are associated with elevated RS and may indicate a shift toward NHEJ-mediated repair under stress condi-tions. Our study provides a refined approach to quantify RS and sheds light on its broader impact on DNA repair network dynamics. ]]> http://www.cell-stress.com/researcharticles/2025a-forveille-cell-stress/ Mon, 11 Aug 2025 18:23:28 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9687
Sabrina Forveille, Marion Leduc, Allan Sauvat, Guido Kroemer and Oliver Kepp

Antibody-drug conjugates (ADCs) offer a strategy for targeted delivery of cytotoxic agents to cancer cells. In this study, we investigated the mechanism of action of datopotamab deruxtecan, an ADC composed of a monoclonal antibody targeting tumor-associated calcium signal transducer 2 (TACSTD2, also known as trophoblast cell-surface antigen-2 (TROP2)) conjugated to the topoisomerase I inhibitor DXd. Datopotamab deruxtecan reduced the viability of human osteosarcoma U2OS cells engineered to express TROP2, but had no effect on their parental counterparts, which only expressed the CALR-GFP biosensor. In TROP2-expressing cells, it triggered the translocation of CALR-GFP from the ER to the cell periphery. Both datopotamab deruxtecan and its DXd payload elicited several features characteristic of immunogenic cell death (ICD), including detectable calreticulin exposure on the cell surface, release of high-mobility group box 1 (HMGB1), and ATP secretion into the culture medium. Importantly, the TROP2-targeted ADC also exerted a bystander antitumor effect on parental U2OS cells (lacking TROP2 expression) co-cultured with TROP2-expressing U2OS cells. These findings demonstrate that datopotamab deruxtecan delivers a cytotoxic payload capable of inducing hallmark features of ICD in vitro. ]]> http://www.cell-stress.com/researcharticles/2025-jalmukhambetova-cell-stress/ Thu, 07 Aug 2025 13:56:37 +0000 Cell Stress https://www.cell-stress.com/?post_type=researcharticles&p=9683
Aiman Jalmukhambetova, Aidana Baltabekova, Aizhan Tolebay, Nargiz Rakhimgerey, Ferdinand Molnár, Tri Thanh Pham, Agata N. Burska and Dos D. Sarbassov

An imbalanced production of reactive oxygen species (ROS) is linked to various aspects of cancer development, including cytoskeletal remodelling. However, the relationship between ROS, actin and cellular stiffness remains controversial. Here, we show that oxidative stress increases cortical stiffness in pre-apoptotic colon and pancreatic cancer cells via localized F-actin polymerization in the apical cortex — independent of changes in total F-actin levels. Using atomic force microscopy and flow cytometry, we demonstrate this effect across multiple ROS inducers: the combination of arsenic trioxide and D-enantiomer of vitamin C, hydrogen peroxide, and rotenone. These findings explain previously debated relationships on how ROS influence actin organization, which may affect cellular stiffness. By separating total from cortical actin effects, our study reveals a redox-sensitive mechanism that governs cytoskeletal remodelling and may impair cancer cell migration. ]]>