Cell Cycle最新文献

{"title":"A fasting-mimicking environment enhances procaspase-activating compound 1 in 2D and 3D glioma cell models.","authors":"Kiarn Roughley, Abass Khochaiche, Ari Landstra, Michael Valceski, Carolyn Hollis, Michael Lerch, Stéphanie Corde, Moeava Tehei","doi":"10.1080/15384101.2026.2614017","DOIUrl":"10.1080/15384101.2026.2614017","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is the most common form of malignant brain cancer and is generally approached with palliative intent. Preclinical studies suggest that short-term fasting may be an effective tool for enhancing existing cancer therapies by disrupting the glucose-dependent, oncogenic phenotype of many cancers. In this study, we investigated whether a fasting-mimicking environment (FME) enhances the efficacy of an emerging proapoptotic drug, procaspase-activating compound 1 (PAC-1), in 2D and 3D GBM cell models. Ad libitum food consumption (Fed) and FME conditions were simulated <i>in vitro</i> by modifying glucose, ketone and serum concentrations. The FME conditions enhanced PAC-1 in U87-MG, T98G and 9L-GS monolayer experiments by significantly reducing the PAC-1 50% inhibitory concentration (IC₅₀), delaying cell growth and increasing apoptosis. Similarly, in the 3D spheroid models, the minimum concentration of PAC-1 required to reduce U87-MG and 9L-GS spheroid area was lower in the FME conditions than the Fed conditions. Additionally, we discovered that serum restriction was primarily responsible for the FME-induced PAC-1 enhancement. These finding are the first to demonstrate that fasting-mimicking conditions sensitize 2D and 3D glioma cell models to PAC-1, supporting the use of short-term fasting as a low-cost and widely accessible strategy for enhancing cancer therapies.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-12"},"PeriodicalIF":3.9,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Goosecoid facilitates the metastasis of pancreatic adenocarcinoma by enhancing EMT and stemness via regulating TGF-β/SMAD2/3 signaling.","authors":"Yong Meng, Rui Li, Weirong Jiang, Wenhao Chen, Zhen Xu, Zhiwen Li, Yisen Hou, Tianfei Wang","doi":"10.1080/15384101.2025.2604772","DOIUrl":"10.1080/15384101.2025.2604772","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignant tumor of the gastrointestinal tract. Goosecoid (GSC), translated from a homeobox gene, is a protein participating in metastasis of assorted tumors. This study explores the role of GSC implicated in tumor metastasis, in PAAD progression. GSC expression in PAAD tissues and cells were tested by quantitative polymerase chain reaction (PCR) and western blot. GSC mRNA and protein expressions were elevated in PAAD tissues and cells. The impacts of GSC depletion or upregulation on PAAD cell proliferation, migration, invasion, cell cycle, and apoptosis were determined by colony formation assay, transwell assay, and flow cytometry. E-cadherin and N-cadherin expressions were tested through immunofluorescence to evaluate the epithelial-mesenchymal transition (EMT) process. The results showed that GSC depletion notably restrained cell proliferative and migratory capabilities and cell cycle, declined MMP2 and MMP9 activity, suppressed EMT process, and enhanced cell apoptosis. Nevertheless, GSC overexpression showed the opposite functions. Stem cell markers CD44 and CD133 were suppressed by GSC depletion and enhanced by GSC overexpression. Additionally, a sphere formation assay was implemented to test cell stemness. The levels of key proteins on TGF-β signaling were tested by western blot. GSC could activate TGF-β signaling in cells by promoting SMAD2/3 phosphorylation. The pathway inhibitor SIS3 notably counteracted the functions on cell malignant phenotypes induced by GSC overexpression. Moreover, xenograft tumor-bearing mouse models were established using male BALB/c nude mice to explore the effects of GSC knockdown on tumor growth and metastasis <i>in vivo</i>, and we found that GSC knockdown inhibited PAAD tumor growth and metastasis in xenograft models. GSC is expressed at a high level in PAAD and can facilitate PAAD metastasis by enhancing EMT and stemness via regulating TGF-β/SMAD2/3 signaling.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-17"},"PeriodicalIF":3.9,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locus-specific transcriptional regulation of transposable elements by p53.","authors":"Julia M Freewoman, Andrew J Rosato, Thomas M Russell, Feng Cui","doi":"10.1080/15384101.2026.2614019","DOIUrl":"10.1080/15384101.2026.2614019","url":null,"abstract":"<p><p>The tumor suppressor p53 protects genomic integrity in part by regulating transposable elements (TEs). Studies of p53-TE interactions rely on synthetic DNA and reporter assays, estimating expression only at the family or subfamily level and lacking locus-specific resolution. To address this limitation, we developed a computational pipeline for ChIP-seq and RNA-seq analysis that employs advanced algorithms to accurately assign short reads mapping to multiple genomic locations. This approach enables precise quantification of TE transcripts at the locus level. By integrating p53 ChIP peaks with differentially expressed TE transcripts, we performed a global analysis of TE expression upon p53 binding. Applying this framework to lung fibroblast IMR90 and colon cancer HCT116 cells treated with p53 activators, we observed a striking pattern: TEs were predominantly activated in normal IMR90 cells but repressed in HCT116 cancer cells. Further analysis of 24 transcriptomes and 10 cistromes confirmed this trend as a distinguishing hallmark between normal and cancer cells. At the family level, normal cells showed broad TE upregulation, whereas cancer cells exhibited selective repression of Alu and LINE elements. These findings provide the first comprehensive, locus-specific view of TE expression associated with p53 binding, implicating a potential role of chromatin context in TE regulation.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-17"},"PeriodicalIF":3.9,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes in cellular mechanics and membrane microviscosity during migration of colorectal cancer cells.","authors":"Liubov Shimolina, Yuri M Efremov, Alexandra Khlynova, Nadezhda Ignatova, Marina K Kuimova, Peter S Timashev, Marina Shirmanova","doi":"10.1080/15384101.2026.2614023","DOIUrl":"10.1080/15384101.2026.2614023","url":null,"abstract":"<p><p>The ability of tumor cells to migrate and invade adjacent tissue is a key property underlying the metastatic process. To ensure greater deformability and to facilitate movement, migratory cells undergo multiple changes in biophysical parameters, including those of stiffness and membrane viscosity. However, reports on correlations between cell motility and stiffness, or between cell motility and membrane microviscosity are rather limited and conflicting. Here, using atomic force microscopy (AFM) and fluorescence lifetime imaging (FLIM), we have investigated alterations in the mechanical properties of cancer cells and in the microviscosity of their plasma membranes that are associated with the migration process. It was found that upon activation of migration either through a \"wound healing\" test or by inducing epithelial-mesenchymal transition, human colorectal cancer cells undergo profound biomechanical remodeling characterized by simultaneous decreases in cell stiffness and in plasma membrane microviscosity. Our findings, therefore, support the results of previous studies that have shown cell softening and membrane fluidization to be critical adaptive responses enabling cell movement and that these can be regarded as potential biomarkers of tumor cell motility, offering scope for identifying new therapeutic targets.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-19"},"PeriodicalIF":3.9,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between autophagy, p16^INK4a, and senescence in tumor cells: a systematic review.","authors":"Ahmet Alperen Palabiyik, Esra Palabiyik","doi":"10.1080/15384101.2025.2597989","DOIUrl":"10.1080/15384101.2025.2597989","url":null,"abstract":"<p><p>Autophagy and cellular senescence are fundamental determinants of tumor cell fate. p16^INK4a has emerged as a key regulator at the intersection of these processes, yet its mechanistic role in the autophagy - senescence axis remains incompletely defined. Understanding this interaction is essential for identifying novel therapeutic opportunities in oncology. A systematic literature search was conducted across PubMed, Web of Science, and Scopus for studies published between January 2000 and April 2025, yielding 10 eligible studies after the application of predefined criteria. Evidence shows a dual role of autophagy in tumor biology. In some models, autophagy increased p16^INK4a and senescence-associated β-gal activity, leading to stable growth arrest. Under stress conditions, however, it supported tumor cell survival despite senescence signals. Mechanistically, p16^INK4a acted both upstream, modulating autophagic flux, and downstream, as an effector of autophagy-induced senescence. Study heterogeneity limited direct comparisons. Autophagy and p16^INK4a interact bidirectionally to regulate senescence, representing a critical axis that can shift tumor cells between suppression and survival. Future research should prioritize standardized protocols, longitudinal models, and therapeutic evaluations to clarify whether targeting this pathway can be translated into effective cancer interventions.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-11"},"PeriodicalIF":3.4,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of fibronectin in the tumor microenvironment - implications for immunotherapy.","authors":"Adrian Kasprzak, Andrzej Wasilewski, Krystian Skowron, Zofia Sowa, Kacper Biela, Marianna Fendor, Małgorzata Pupek","doi":"10.1080/15384101.2026.2735503","DOIUrl":"10.1080/15384101.2026.2735503","url":null,"abstract":"<p><p>Contemporary models of tumor progression highlight the key role of the tumor microenvironment (TME) and the extracellular matrix (ECM) in regulating angiogenesis, metastasis, and immune resistance. Among ECM components, oncofetal fibronectin (FN) isoforms containing the EDA and EDB domains are of particular interest because they are highly expressed in solid tumors but absent from normal adult tissues. This review article synthesizes current data on the pathophysiological functions of FN variants in oncogenesis. Particular attention was paid to their role in pathological vascular remodeling, the induction of epithelial-mesenchymal transition (EMT), the formation of pre-metastatic niches, and the generation of an immunosuppressive environment. The study also critically assesses the clinical significance of FN as a biomarker and a potential target for new therapies in breast cancer, ovarian cancer and glioblastoma. The prospects for the use of innovative stromal strategies - including antibody-drug conjugates (ADCs) and immunocytokines - to overcome resistance to standard immunotherapy are also highlighted.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-18"},"PeriodicalIF":3.9,"publicationDate":"2026-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.","authors":"","doi":"10.1080/15384101.2026.2707748","DOIUrl":"10.1080/15384101.2026.2707748","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-i"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From dysbiosis to precision oncology: translational role of the microbiome in gastrointestinal cancer.","authors":"Mathab Adam, Adwaith Venugopal, Amir Almohana, Mohammad Awadallah, Paanchali Purohit, Aliza Abid, Elenza Jose, Abirami Rajendiran, Priyanka Banka, Charishma Ilipilla, Fnu Bhuvan, Manju Rai","doi":"10.1080/15384101.2026.2725418","DOIUrl":"10.1080/15384101.2026.2725418","url":null,"abstract":"<p><p>Gastrointestinal (GI) cancers, including colorectal, gastric, pancreatic, hepatocellular, and esophageal malignancies, remain a leading cause of cancer-related mortality worldwide. Emerging evidence identifies the gut microbiome as a critical regulator of GI carcinogenesis, influencing tumor initiation, immune evasion, therapeutic response, and clinical outcomes through inflammation, genotoxicity, metabolic reprogramming, and epithelial barrier disruption. Importantly, biological rationale, clinical evidence, and translational opportunities differ across GI tumor types. Specific taxa, including <i>Fusobacterium nucleatum</i>, enterotoxigenic <i>Bacteroides fragilis</i>, pks⁺ <i>Escherichia coli</i>, and <i>Helicobacter pylori</i>, exhibit tumor-specific oncogenic roles with causal evidence ranging from associative to guideline-validated. Microbiome-based biomarkers, including composite multi-taxon models and signatures predictive of immune checkpoint inhibitor response, are evaluated using a four-tier framework (preclinical, associative, near-clinical, and validated). Microbiome-targeted therapies, including probiotics, fecal microbiota transplantation, dietary modulation, and engineered microbial therapeutics, are critically appraised according to clinical evidence and translational readiness. Advances in spatial microbiomics, single-cell analysis, multi-omics, and artificial intelligence may further accelerate microbiome-based precision oncology. This review provides a translationally stratified synthesis of microbiome-GI cancer interactions and their implications for precision oncology.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-29"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: A novel role for fanconi anemia (FA) pathway effector protein FANCD2 in cell cycle progression of untransformed primary human cells.","authors":"","doi":"10.1080/15384101.2026.2624973","DOIUrl":"10.1080/15384101.2026.2624973","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EP300 attenuates ferroptosis and stimulates proliferation, migration, and fibrosis of keloid fibroblasts <i>via</i> YY1/GPX4 axis.","authors":"Jun Jin, Kai Wang, Chenxi Lu, Chenghao Yao, Feng Xie","doi":"10.1080/15384101.2026.2627885","DOIUrl":"10.1080/15384101.2026.2627885","url":null,"abstract":"<p><p>The aim of this investigation was to identify the hub genes associated with ferroptosis in keloid. We analyzed the correlation between differentially expressed genes Yin Yang-1 (YY1) and glutathione peroxidase-4 (GPX4) with keloid by quantitative Real‑Time PCR and Western blot. Molecular biological experiments were conducted to identify the role of YY1 and GPX4 in human keloid fibroblasts (HKFs). glutathione and oxidized glutathione kit, Malondialdehyde Assay Kit and C11-BODIPY (581/591) fluorescence probe were applied to monitor ferroptosis. Gain-of-function and loss-of-function assay demonstrated that YY1 regulated proliferation, migration, fibrosis of HKFs <i>in vitro</i>. YY1 bind to the promoter sequence of target gene GPX4. YY1-induced HKFs ferroptosis was dependent on GPX4 pathway. Furthermore, we discovered that the UCSC Genome Browser Database included an enrichment of H3K27ac signals at the YY1 promoter region. The inhibition of proliferation, migration, fibrosis, and the activation of ferroptosis in knockdown of YY1 HKFs was reversed by EP300 overexpression.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"25 1","pages":"1-16"},"PeriodicalIF":3.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}