Biology of the Cell最新文献

{"title":"Rearrangement of the Cell Chaperone Machinery in Human Fibrosarcoma HT1080 Cells With the Knocked-Out HSP90AA1 Gene Encoding Hsp90α.","authors":"Viktoria Petrenko, Veronika Vrublevskaya, Yuri Skarga, Mariya Zhmurina, Oleg Morenkov","doi":"10.1111/boc.70064","DOIUrl":"https://doi.org/10.1111/boc.70064","url":null,"abstract":"<p><strong>Background: </strong>Two isoforms of the 90-kDa heat shock protein (Hsp90), stress-inducible Hsp90α and constitutively expressed Hsp90β, function in mammalian cells as molecular chaperones that promote the folding of specific client proteins involved in essential cellular processes and regulatory pathways. A number of Hsp90 client proteins take part in cancer progression, and the inhibition of Hsp90 induces the degradation of oncogenic client proteins and cancer cell death. Hsp90 inhibitors specific for individual Hsp90 isoforms have a significant potential for the development of anticancer therapeutics due to reduced toxicity. Cells with knocked-out genes encoding Hsp90 isoforms represent excellent cellular models to investigate the rearrangement of the cell chaperone machinery in response to the suppression/loss of the Hsp90 isoforms.</p><p><strong>Results: </strong>Recently, we have shown that the knockout of the HSP90AA1 gene encoding Hsp90α in human fibrosarcoma HT1080 cells does not affect basic cellular processes in normal and stressful conditions, which suggests an adaptation of the cell chaperone machinery to the loss of Hsp90α. Here, we demonstrated that the lack of Hsp90α in HT1080 cells leads to an up-regulation of the constitutively expressed Hsp90β and several important Hsp90 co-chaperones (Aha1, Hop, and others). The expression of the major chaperones of the Hsp70 machinery (Hsp70-1, Hsp70-2, Hsc70) was also significantly induced. The components of the prefoldin-chaperonin folding arm and PFDL, R2TP, and R2SP complexes, as well as the major mitochondrial chaperones, were also largely up-regulated in Hsp90α-KO cells, while the expression of ER-resident chaperones/co-chaperones was either repressed or did not change.</p><p><strong>Conclusions and significance: </strong>We demonstrated here for the first time an adaptation of the cell chaperone machinery to the loss of the Hsp90α chaperone, which may be important for understanding the molecular mechanisms of action of Hsp90α-specific inhibitors and elaborating new therapy strategies in combating cancer, including the combination of Hsp90α-targeted therapy.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 5","pages":"e70064"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delta-Cell Area is Unchanged in Human Pregnancy: Evidence From Immunohistochemistry.","authors":"Faheem Seedat, Neva Kandzija, Edward Drydale, Katie Holden, James Bancroft, John A Todd, M Irina Stefana, Manu Vatish","doi":"10.1111/boc.70067","DOIUrl":"https://doi.org/10.1111/boc.70067","url":null,"abstract":"<p><strong>Aim: </strong>Pancreatic islet δ-cells produce somatostatin, a paracrine regulator of insulin and glucagon secretion within islets. Although adaptive changes in α- and β-cell populations during pregnancy have been described in both animals and humans, data on δ-cell plasticity are sparse and entirely lacking in human pregnancy. We aimed to determine whether pancreatic islet δ-cell mass undergoes morphological adaptation during human pregnancy.</p><p><strong>Methods and results: </strong>Formalin-fixed paraffin-embedded pancreatic tissue from pregnant (n = 7) and non-pregnant (n = 7) donors was analysed. Sections were immunolabelled for somatostatin to identify δ cells, and whole-slide quantitative analysis was performed using an unbiased automated imaging pipeline. δ-cell area was measured across the entire pancreatic sections and compared between groups. In contrast to previously reported expansion of α- and β-cell populations in pregnancy, δ-cell area was not significantly different between pregnant and non-pregnant donors. No quantitative architectural alterations in δ-cell distribution within islets were observed.</p><p><strong>Conclusion: </strong>Pancreatic δ-cell area does not increase during human pregnancy. These findings demonstrate that endocrine cell plasticity within the maternal pancreas is selective and does not uniformly involve all islet cell subtypes.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 5","pages":"e70067"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833042","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":"STAT Signaling and Its Anti-Apoptotic Effects in Dehydrated Xenopus laevis.","authors":"Yulia Biggar, Akshay A Kamath, Sarah A Breedon, Kenneth B Storey","doi":"10.1111/boc.70069","DOIUrl":"https://doi.org/10.1111/boc.70069","url":null,"abstract":"<p><p>Xenopus laevis survives seasonal droughts by entering a hypometabolic state known as aestivation. One of the mechanisms employed by X. laevis to mitigate aestivation-induced tissue atrophy is gene regulation of pro-survival proteins. We further expand on the role of anti-apoptotic signaling in X. laevis by investigating the effect of signal transducer and activator of transcription (STAT) signaling on downstream anti-apoptotic genes in control and dehydrated liver and skeletal muscle of X. laevis. Herein, we found that STAT signaling is differentially regulated between tissues. STAT3 signaling in the liver and STAT5 signaling in skeletal muscle lead to the selective upregulation of downstream anti-apoptotic proteins. Additionally, pro-apoptotic STAT1 signaling is found to be attenuated in both tissues during dehydration stress. Overall, our results indicate an important role for anti-apoptotic proteins during dehydration stress and their contribution in mitigating aestivation-induced atrophy.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 5","pages":"e70069"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810392","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":"Correction to \"Ultrastructure, Polarity, and Reproduction of the Golgi Apparatus\".","authors":"","doi":"10.1111/boc.70065","DOIUrl":"https://doi.org/10.1111/boc.70065","url":null,"abstract":"","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 5","pages":"e70065"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Activity Localization in the Skeletal Muscle and Its Individual Fibers Across Tetrapods.","authors":"Unmod Senapati, Subhasmita Rout, Sunil Pani, Bijayashree Sahu, Gourabamani Swalsingh, Punyadhara Pani, Benudhara Pati, Prabhat Kumar Rout, Rajesh Kumar Mohapatra, Suryakant Mishra, Naresh Chandra Bal","doi":"10.1111/boc.70066","DOIUrl":"https://doi.org/10.1111/boc.70066","url":null,"abstract":"<p><p>Mitochondria exhibit a complex spatially organized distribution within muscle, tailored to the energy requirements of ATPases and contractile filaments, which exhibit precise intracellular positioning. Mitochondrial distribution varies across longitudinal and transverse axes as well as based on fiber composition within the muscle. The differential mitochondrial capacity can be localized in muscle by succinate dehydrogenase (SDH) activity. Given the distinct energy requirements of the fore-limb and hind-limb muscles, this study aimed to investigate the distribution of mitochondrial activity within individual fibers and their composition within fascicles across different tetrapod taxa. We analyzed pectoralis and gastrocnemius from toad, garden lizard, duck, pigeon, quail, chicken, rat, rabbit, goat, and buffalo. The study revealed unique patterns of mitochondrial activity distribution within the same muscle across various tetrapods. Toad and lizard muscles showed mostly fibers with intermediate SDH-activity (SDH^Int) in both muscles. The muscles only from birds and mammals exhibited fibers with negligible SDH-activity termed SDH^Low, which might indicate that such fibers are evolutionarily more recent. Interestingly, avian pectoralis showed a very unique fiber composition compared to mammals, which displayed a mosaic pattern of different fibers. Among mammals, slow-grazers (buffaloes, goats) had higher percentages of SDH^High and SDH^Int fibers, whereas sprint-runners (rats, rabbits) possessed a high abundance of SDH^Low fibers. These findings provide evidence for localized mitochondrial enrichment as an adaptation strategy to create muscle group heterogeneity. SUMMARY STATEMENT: This study characterizes the spatial distribution of mitochondrial activity in skeletal muscle across tetrapods, from the single-fiber scale to the fascicular level.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 5","pages":"e70066"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated 2D-3D Proteomic Profiling Identifies MLK4 as a Microenvironment-Responsive Regulator of Chemotherapeutic Resistance in Human Glioblastoma Cells.","authors":"Wannawat Khotchawan, Pakorn Ruengket, Pakpoom Kheolamai, Sith Sathornsumetee, Chomdao Sinthuvanich, Chanchao Lorthongpanich, Surapol Issaragrisil","doi":"10.1111/boc.70068","DOIUrl":"https://doi.org/10.1111/boc.70068","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic resistance is a major cause of treatment failure in glioblastoma (GBM), highlighting the need for physiologically relevant models to identify actionable resistance mechanisms. While two-dimensional (2D) cultures are widely used for target discovery, they poorly represent the tumor microenvironment. In contrast, three-dimensional (3D) spheroid cultures better recapitulate spatial heterogeneity, hypoxic gradients, and stress-adaptive signaling observed in tumors.</p><p><strong>Methods: </strong>We applied an integrated 2D-3D quantitative proteomic approach to identify microenvironment-dependent regulators of chemoresistance in GBM. Proteomic profiling was performed in U87MG and U251MG cells grown as 2D monolayers or 3D spheroids. Differentially expressed proteins were validated by quantitative RT-PCR, and functional studies were conducted using genetic depletion followed by assessment of temozolomide (TMZ) sensitivity.</p><p><strong>Results: </strong>Comparative analysis identified 13 proteins consistently differentially expressed between 2D and 3D cultures: NDUFB5, RNGTT, MLK4, SYN1, DDX5, EIF2AK2, ITGA1, ZNF33B, ZNF343, WDR19, JPH3, CCT8L2, and FNDC3A. Among these, Mixed Lineage Kinase 4 (MLK4) showed strong and reproducible upregulation in 3D spheroids in both GBM cell lines. Genetic depletion of MLK4 significantly increased TMZ sensitivity without affecting basal cell viability, suggesting a specific role in therapy response. Notably, MLK4 expression was induced only under 3D conditions.</p><p><strong>Conclusion: </strong>MLK4 functions as a microenvironment-responsive regulator of chemoresistance in GBM. These findings demonstrate that 3D culture systems reveal clinically relevant resistance pathways not detectable in conventional 2D models and highlight 3D proteomic profiling as a powerful strategy for identifying therapeutically actionable targets.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 5","pages":"e70068"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810363","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":"Sibling Rivalry.","authors":"Christopher Thomas","doi":"10.1111/boc.70063","DOIUrl":"https://doi.org/10.1111/boc.70063","url":null,"abstract":"","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 4","pages":"e70063"},"PeriodicalIF":2.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Interview With Louise Fougère. Winner of the SBCF PhD Award","authors":"Paul Trevorrow,&nbsp;Louise Fougere","doi":"10.1111/boc.70061","DOIUrl":"10.1111/boc.70061","url":null,"abstract":"","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Morphological Cell Studies","authors":"Albert Oppel","doi":"10.1111/boc.70057","DOIUrl":"10.1111/boc.70057","url":null,"abstract":"","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healing Wounds","authors":"L. Anger,&nbsp;A. Harrouet,&nbsp;M. Hautefeuille,&nbsp;M. A. Fardin","doi":"10.1111/boc.70056","DOIUrl":"10.1111/boc.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Wound healing has long provided a framework for studying cell and tissue dynamics, yet early contributions are often overlooked. Revisiting research from the late 19th to mid-20th centuries reveals enduring questions on migration versus proliferation, individual versus collective motion, and chemical versus mechanical drivers. Concepts such as contractility, collective motility, and contact inhibition illustrate the continuity of debate across generations. By reconnecting these foundational studies with modern advances, we highlight persistent gaps and offer historical context to guide future research.</p>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}