FEBS Open Bio最新文献

{"title":"Suppression of lung adenocarcinoma migration through organelle alkalization by human lactoferrin – albumin fusion","authors":"Hana Nopia,&nbsp;Masahiro Kimura,&nbsp;Daisuke Kurimoto,&nbsp;Atsushi Sato","doi":"10.1002/2211-5463.70237","DOIUrl":"10.1002/2211-5463.70237","url":null,"abstract":"<p>The fusion of human serum albumin with human lactoferrin (hLF-HSA) exerts strong anti-migratory effects in human lung adenocarcinoma cells through matrix metalloproteinase 1 (MMP1) downregulation. We demonstrate that hLF-HSA disrupts organelle pH homeostasis via Na⁺/H⁺ exchanger 7 (NHE7) upregulation, inducing organelle alkalization in the Golgi apparatus. This organelle dysfunction alters the Golgi-mediated secretome, leading to MMP1 downregulation and suppression of cell migration. hLF-HSA-induced MMP1 downregulation also reverses epithelial-mesenchymal transition (EMT), further suppressing migration. Additionally, hLF-HSA-driven activation of caveolae-mediated endocytosis (CavME) signaling downregulated MMP1 expression without NHE7 upregulation. These findings highlight that hLF-HSA–mediated disruption of organelle pH regulation and CavME activation represents a potential strategy to suppress cancer cell migration.</p><p>\u0000 </p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1786-1800"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life high-fat diet exposure increases Achilles tendon stiffness and induces transcriptomic alterations","authors":"Heyong Yin,&nbsp;Ziyang Yuan,&nbsp;Wenli Jiang,&nbsp;Ai Guo","doi":"10.1002/2211-5463.70253","DOIUrl":"10.1002/2211-5463.70253","url":null,"abstract":"<p>High-fat diet (HFD) exposure is a recognized risk factor for tendinopathy and impaired tendon healing in adults, yet its effects on baseline tendon properties following early-life exposure remain poorly understood. In this study, we investigated the structural, biomechanical, and transcriptomic characteristics of Achilles tendons in 12-week-old rat offspring born to dams fed an HFD or a normal diet during gestation. Compared with controls, HFD-exposed tendons exhibited a significant reduction in anteroposterior diameter on sagittal ultrasound imaging. However, histological assessment revealed comparable cellular density and collagen fiber organization between groups. Biomechanically, HFD exposure was associated with a significant increase in tendon stiffness, while the maximum tensile load was not significantly altered. Transcriptomic profiling identified 980 differentially expressed genes, including a marked downregulation of key tenogenic markers such as Scx and Eya2, along with an enrichment of pathways related to extracellular matrix remodeling and inflammation. Gene set enrichment further revealed an upregulation of inflammatory response, adipogenesis, and osteoblast differentiation signatures. Together, these findings demonstrate that early-life HFD exposure induces biomechanical and molecular alterations in intact Achilles tendons, suggesting compromised tendon quality that may increase susceptibility to mechanical overload and injury later in life.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1741-1751"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Career Reviewer Hub: Paving the way for the next generation of peer reviewers","authors":"Sara Fuentes,&nbsp;Miguel A. De la Rosa","doi":"10.1002/2211-5463.70335","DOIUrl":"https://doi.org/10.1002/2211-5463.70335","url":null,"abstract":"<p><i>FEBS Open Bio</i> is pleased to announce the launch of the Early Career Reviewer Hub, a new initiative designed to provide professional training and first-hand experience to Early Career Researchers (ECRs) interested in taking part in the peer-review process. We hope that, through this new programme and our focus on Research Protocols, we will continue to support and contribute to the professional development of early career molecular life scientists.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1634-1636"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-based proteomic profiling reveals context-dependent changes in BCL2-associated signaling during taxane therapy in breast cancer patients","authors":"Saira Munshani,&nbsp;Eiman Y. Ibrahim,&nbsp;Rozalyn L. Rodwin,&nbsp;Leah M. Ferrucci,&nbsp;Kim Blenman,&nbsp;Maryam Lustberg,&nbsp;Barbara E. Ehrlich","doi":"10.1002/2211-5463.70239","DOIUrl":"10.1002/2211-5463.70239","url":null,"abstract":"<p>The quality of life for many cancer survivors is compromised due to severe, long-lasting side effects of chemotherapy. As part of a pilot, prospective, non-interventional study to examine the side effects of chemotherapy in breast cancer patients, we examined the change in protein expression in blood collected from patients before and after treatment with taxanes for 12 weeks. Protein expression was measured with reverse phase proteomic arrays (RPPA), which revealed divergent changes in apoptosis, senescence, and calcium signaling-related proteins depending on treatment setting (neoadjuvant vs. adjuvant). The largest change identified was BCL2 (B-cell lymphoma 2), a founding member of the BCL2 family of proteins that regulate apoptosis. Other proteins regulated by BCL2, including RB1 (retinoblastoma protein 1) and NLRP3 (NLR family pyrin domain containing 3) changed significantly over the course of treatment. These differences are consistent with intracellular calcium signaling dysregulation and activation of stress-response pathways that overlap with senescent-associated secretory phenotype (SASP)-like signaling, which has been implicated in cancer recurrence. To contextualize these observations, we generated Kaplan–Meier survival curves using publicly available proteomics data from The Cancer Proteome Atlas (TCPA). This work aims to demonstrate how blood-based proteomics can serve as a non-invasive method to monitor systemic physiological shifts during cancer therapy, offering a framework for generating hypotheses about chemotherapy timing and long-term outcomes.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1801-1812"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying transcription factors controlling the basal expression of human MRP4 highlights a substantial role for Sp1","authors":"Debora Singer,&nbsp;Angelique Kragl,&nbsp;Katrin Ziems,&nbsp;Juliane Glaubitz,&nbsp;Sophie Grammbauer,&nbsp;Susanne Hildebrandt,&nbsp;Mladen V. Tzvetkov,&nbsp;Gabriele Jedlitschky","doi":"10.1002/2211-5463.70245","DOIUrl":"10.1002/2211-5463.70245","url":null,"abstract":"<p>The multidrug resistance protein 4 (MRP4/ABCC4) is a versatile efflux pump, known to transport several drugs but also signaling molecules such as cyclic nucleotides and lipid mediators. Based on this substrate spectrum and its broad tissue distribution, MRP4 plays a significant physiological and pathophysiological role in both the cardiovascular and oncological fields. However, the determinants of its gene expression are still incompletely defined. This study aimed to identify key regulatory elements and transcription factors that are essential for basal <i>MRP4</i> expression. Using luciferase reporter assays with a series of 5′-deletion constructs, we identified a region upstream of the transcription start site as crucial for basal expression across diverse cell types. This region is evolutionary highly conserved and contains putative binding sites for Sp1 and Ets transcription factors. Site-directed mutagenesis of both binding elements resulted in a significant decrease in the promoter activity in HeLa and megakaryoblastic M07e cells. The binding of Sp1 to this region was further confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays. Finally, siRNA knockdown of Sp1 led to a significant decrease in MRP4 protein levels and function. In summary, we show that Sp1 binds to the <i>MRP4</i> promoter and plays an essential role in the basal expression of <i>MRP4</i>, with Ets factors also potentially cooperating in this regulation.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1825-1839"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics simulations of positively selected codons in FcγRI reveal novel biochemical binding properties","authors":"David A. Young,&nbsp;Omar Arias-Gaguancela,&nbsp;Fiona Gibson,&nbsp;Morgan Grainger,&nbsp;Jodie Score,&nbsp;Amit Nathubhai,&nbsp;Mauricio Cafiero,&nbsp;Lee Richard Machado","doi":"10.1002/2211-5463.70247","DOIUrl":"10.1002/2211-5463.70247","url":null,"abstract":"<p>FcγRI is a high-affinity receptor for IgG, associated with autoimmune disease pathology and determines clinical responses to antibody-based immunotherapies. FcγRI has a complex evolutionary history that is not fully understood, and to address this we explored signatures of positive selection in the receptor's functional gene, <i>FCGR1A,</i> using codon-based selection tests on aligned 1–1 orthologous sequences from placental mammals (<i>n</i> = 32). Signatures of positive selection have occurred at several locations within the gene, with two sites (H¹⁴⁸ (M2a ω 0.997 &amp; M8 ω = 0.993)) and (W¹⁴⁹ (M2a ω = 0.999 &amp; M8 ω = 1.000)) exhibiting highest posterior probabilities, suggesting strong evidence of positive selection; these positions are known to form one of the FcγRI-IgG binding interfaces. We employed ancestral reconstruction to statistically infer prior codon sequences at these sites and identified ancestral H¹⁴⁸P and W¹⁴⁹R codons at different nodes in the phylogeny. Employing molecular dynamics simulations, we determined how evolutionary changes at these sites may have influenced the binding of FcγRI-IgG of modern-day <i>Homo sapiens</i>. Measuring RMSD, free energy, radius of gyration, hydrogen bond formation, and analyzing free energy landscapes, we demonstrate that structural instability between mutant structures vs the WT counterpart; however, overall binding potential increases at position 148, yet decreases at 149 in potential. H¹⁴⁸P protonation at physiological pH remains similar, yet during acidotic calculations, protonation is likely reduced, with predicted reduction in affinity for IgG. While ancestral W¹⁴⁹R substitutions demonstrate an implication for electron conjugation. Examining key sites at this binding FcγRI-IgG interface, our data demonstrate that these two codons have evolved in humans to be relatively insensitive to shifts in pH promoting a more stable interaction with the Fc portion of IgG during diseases that promote acidosis.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1708-1725"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A yeast model of 5-oxoproline accumulation reveals a general toleration to 5-oxoproline","authors":"Pratiksha Dubey,&nbsp;Vaishnavi Sanjayan,&nbsp;Praveen Singh,&nbsp;Shantanu Sengupta,&nbsp;Anand Kumar Bachhawat","doi":"10.1002/2211-5463.70254","DOIUrl":"10.1002/2211-5463.70254","url":null,"abstract":"<p>5-oxoproline (5-OP) or pyroglutamic acid is an intermediate in the degradation arc of the glutathione cycle. It is metabolized into glutamate through the action of the 5-oxoprolinase enzyme, the only enzyme known to act on this metabolite. 5-OP has long been known to be relatively inert with a proposed role as an osomoprotectant. Recent studies on the 5-oxoprolinase enzyme in mammalian cells have, however, shown that knockdown or deletion of 5-oxoprolinase makes mice (and humans) prone to heart failure, an effect ascribed to oxidative stress caused by a twofold increase in 5-OP. To examine the consequences of 5-oxoproline accumulation more rigorously, we created a yeast model for 5-oxoproline accumulation. Using this model, we observed retardation of growth only when intracellular levels of 5-OP were increased 12- to 20-fold over normal levels. Performing an analysis of transcriptomic changes under these conditions, we observed a large number of genes were differentially regulated and while there was no unifying dysregulated pathway, there was an upregulation of various efflux pumps. Ultimately, modulating the expression of these genes by knockout or overexpression highlighted that many of the upregulated genes were involved in the cellular response to 5-OP accumulation. However, our results failed to show any significant oxidative stress response. In conclusion, our study suggests a need to reevaluate previous suppositions of the 5-OP induced oxidative stress response and proposes alternate mechanisms for this effect.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"16 9","pages":"1752-1765"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ionomycin suppresses cancer cell growth by disrupting mitochondrial transcription.","authors":"Lishen Wang, Mingqiang Deng, Dongmei He, Diqin Lai, Dongjun Liu, Dengyong Zhu, Zhenhua Zhang, Peng Tang, Chuanman Zhou, Menghui Yin, Xichen Bao","doi":"10.1002/2211-5463.70297","DOIUrl":"10.1002/2211-5463.70297","url":null,"abstract":"<p><p>The Warburg effect has long suggested that oxidative phosphorylation (OXPHOS) is dispensable for tumor growth. However, recent studies have shown that the mitochondrial RNA polymerase inhibitors IMT1 and IMT1b, which impair OXPHOS, are potent anticancer agents. Here, we demonstrate that ionomycin, a selective ionophore known to modulate mitochondrial homeostasis, similarly inhibits mitochondrial gene expression across cancer cell lines. Specifically, gene expression and nascent RNA profiling revealed a global downregulation of mitochondrial gene transcription in Jurkat T, THP-1, HeLa, and NCI-H441 cells. Thus, we conclude that ionomycin suppressed mitochondrial gene transcription, impaired OXPHOS, and thereby inhibited cancer cell proliferation and growth, providing a novel insight into the function of ionomycin.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic dissection of human ABCE1 in yeast reveals separable requirements for ribosome recycling and suppression of aberrant reinitiation.","authors":"Eriko Nakata, Yuxin Li, Kei Endo, Koichi Ito","doi":"10.1002/2211-5463.70337","DOIUrl":"10.1002/2211-5463.70337","url":null,"abstract":"<p><p>The ATP-binding cassette E1 (ABCE1) protein is an essential factor for ribosome recycling, splitting post-termination ribosomes into subunits for subsequent rounds of translation. Despite high conservation, human ABCE1 (hABCE1) fails to functionally complement the depletion of its essential yeast homolog, Rli1. In this study, we leveraged this species-specificity to dissect the functional architecture of ABCE1. Through analysis of yeast-human chimeric proteins, we identified the N-terminal nucleotide-binding domain (NBD1) as the primary determinant of this incompatibility. To further investigate, we isolated multiple hABCE1 point mutants (revertants) that successfully restored yeast growth. We then developed a novel dual-luciferase reporter assay to quantify aberrant translation reinitiation in the 3'UTR, an event recognized as a direct consequence of ABCE1 deficiency. Notably, while the revertant mutants rescued yeast viability, they failed to suppress aberrant reinitiation, exhibiting levels equivalent to the nonfunctional hABCE1. This genetic uncoupling of viability from the suppression of reinitiation suggests that the canonical ribosome recycling function required for cell growth and the role in preventing aberrant reinitiation have distinct functional thresholds or are genetically separable aspects of ABCE1 activity.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell surface CD11c as a neutrophil aging marker molecule.","authors":"Sophia Koutsogiannaki, Fahd Alhamdan, Erik Malm, Marie Bermudez, Samuel Y Kim, Koichi Yuki","doi":"10.1002/2211-5463.70332","DOIUrl":"10.1002/2211-5463.70332","url":null,"abstract":"<p><p>Neutrophils exhibit substantial functional heterogeneity shaped by both developmental stage and cellular maturation, but their mechanisms remain incompletely defined. CD11c (ITGAX) is traditionally considered as a cell surface marker of dendritic cells. We recently reported that it is highly expressed intracellularly in neutrophils and contributes to their maturation; however, its role at the cell surface is unclear. Here, we showed that surface CD11c expression level was heterogeneous across neutrophils, enabling classification into CD11c^hi and CD11c^-/lo populations. CD11c^hi neutrophils display enhanced phagocytic capacity and features of neutrophil aging, including increased CXCR4 and reduced CD62L expression. Bulk RNA sequencing across the three pediatric age groups revealed that differentially expressed genes (DEGs) between CD11c^hi and CD11c^-/lo neutrophils were observed most in infants followed by preschool age children. Infant neutrophils exhibited reduced phagocytic capacity and distinct gene expression patterns compared to older children. Functional interrogation of candidate genes (ANXA2, COL6A3, DCN) demonstrated their role in regulating phagocytosis without affecting reactive oxygen species production. Machine learning analysis further identified age-dependent ontology of the DEGs associated with cell surface CD11c expression, including pathways related to adhesion, extracellular matrix interactions, stress responses, and metabolic regulation. Integrative network analysis positioned CD11c linked to cytoskeletal remodeling and phagocytosis. Collectively, these findings support a model in which developmental age establishes the baseline transcriptional landscape of neutrophils, while CD11c serves as a marker of neutrophil aging rather than acting as a primary driver of transcriptional reprogramming.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}