European journal of cell biology最新文献

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Innovations in intestinal organoid technology featuring an open apical surface 具有开放根尖表面的肠道类器官技术的创新。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2025-01-15 DOI: 10.1016/j.ejcb.2025.151476
Ye Chen , Yi Wang
{"title":"Innovations in intestinal organoid technology featuring an open apical surface","authors":"Ye Chen ,&nbsp;Yi Wang","doi":"10.1016/j.ejcb.2025.151476","DOIUrl":"10.1016/j.ejcb.2025.151476","url":null,"abstract":"<div><div>Since the development of the three-dimensional (3D) “mini-gut” culture system, adult stem cell-derived organoid technology has rapidly advanced, providing <em>in vitro</em> models that replicate key cellular, molecular, and physiological properties of multiple organs. The 3D intestinal organoid system has resolved many long-standing challenges associated with immortalized or cancer cell cultures, offering unparalleled capabilities for modeling gastrointestinal development and diseases. However, significant limitations remain, including restricted accessibility to the epithelial apical surface for studying host-microbe interactions, interruptions in modeling chronic gastrointestinal diseases due to frequent passaging and dissociation, and the absence of mechanical cues such as peristalsis and luminal flow, which are critical for organ development and function. To address these challenges, recent advancements have introduced Transwell-based monolayer cultures and microfluidic device-based technologies including “organ-on-a-chip” and scaffold-guided 'mini-gut' system. This review highlights these innovations, with a focus on adult stem cell-derived intestinal organoid models that feature an open apical surface and discusses their prospects and challenges for advancing basic research and clinical applications.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 2","pages":"Article 151476"},"PeriodicalIF":4.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002561","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}
引用次数: 0
LRP1 involvement in FHIT-regulated HER2 signaling in non-small cell lung cancer LRP1参与非小细胞肺癌中fhit调节的HER2信号传导。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-26 DOI: 10.1016/j.ejcb.2024.151475
Théophile Ponchel , Emma Loeffler , Julien Ancel , Audrey Brisebarre , Nathalie Lalun , Véronique Dalstein , Anne Durlach , Gaëtan Deslée , Stéphane Dedieu , Myriam Polette , Béatrice Nawrocki-Raby
{"title":"LRP1 involvement in FHIT-regulated HER2 signaling in non-small cell lung cancer","authors":"Théophile Ponchel ,&nbsp;Emma Loeffler ,&nbsp;Julien Ancel ,&nbsp;Audrey Brisebarre ,&nbsp;Nathalie Lalun ,&nbsp;Véronique Dalstein ,&nbsp;Anne Durlach ,&nbsp;Gaëtan Deslée ,&nbsp;Stéphane Dedieu ,&nbsp;Myriam Polette ,&nbsp;Béatrice Nawrocki-Raby","doi":"10.1016/j.ejcb.2024.151475","DOIUrl":"10.1016/j.ejcb.2024.151475","url":null,"abstract":"<div><div>The tumor suppressor fragile histidine triad (FHIT) is frequently lost in non-small cell lung cancer (NSCLC). We previously showed that a down-regulation of FHIT causes an up-regulation of the activity of HER2 associated to an epithelial-mesenchymal transition (EMT) and that lung tumor cells harboring a FHIT<sup>low</sup>/pHER2<sup>high</sup> phenotype are sensitive to anti-HER2 drugs. Here, we sought to decipher the FHIT-regulated HER2 signaling pathway in NSCLC. Transcriptomic analysis of tumor cells isolated from NSCLC revealed the endocytic receptor low density lipoprotein receptor-related protein 1 (LRP1), a central regulator of membrane trafficking and cell signaling, as a potential player of this signaling. In a cohort of 80 NSCLC assessed by immunohistochemistry, we found a significant association between a low FHIT expression and a high pHER2 and LRP1 expression by tumor cells. Experiments of FHIT silencing showed that FHIT regulated LRP1 expression both at the mRNA and protein levels in lung cell lines. Analyzing the relationship between LRP1 and HER2, we observed that an anti-HER2 targeted therapy reversed LRP1 overexpression induced by FHIT silencing whereas LRP1 silencing did not affect HER2 activity. Studying the functional role of LRP1, we showed that cell proliferation and invasion induced by FHIT silencing were LRP1-dependent. In addition, we found that the induction of vimentin upon FHIT inactivation was counteracted by LRP1 silencing. These results suggest that LRP1 acts downstream of HER2 to induce EMT and tumor progression following FHIT loss. Dual targeting of HER2 and LRP1 might represent a therapeutic strategy to more efficiently inhibit HER2 signaling in FHIT-negative NSCLC.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151475"},"PeriodicalIF":4.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926874","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}
引用次数: 0
Intestinal organoids: The path towards clinical application 肠道类器官:走向临床应用之路。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-25 DOI: 10.1016/j.ejcb.2024.151474
Hady Yuki Sugihara, Ryuichi Okamoto, Tomohiro Mizutani
{"title":"Intestinal organoids: The path towards clinical application","authors":"Hady Yuki Sugihara,&nbsp;Ryuichi Okamoto,&nbsp;Tomohiro Mizutani","doi":"10.1016/j.ejcb.2024.151474","DOIUrl":"10.1016/j.ejcb.2024.151474","url":null,"abstract":"<div><div>Organoids have revolutionized the whole field of biology with their ability to model complex three-dimensional human organs <em>in vitro</em>. Intestinal organoids were especially consequential as the first successful long-term culture of intestinal stem cells, which raised hopes for translational medical applications. Despite significant contributions to basic research, challenges remain to develop intestinal organoids into clinical tools for diagnosis, prognosis, and therapy. In this review, we outline the current state of translational research involving adult stem cell and pluripotent stem cell derived intestinal organoids, highlighting the advances and limitations in disease modeling, drug-screening, personalized medicine, and stem cell therapy. Preclinical studies have demonstrated a remarkable functional recapitulation of infectious and genetic diseases, and there is mounting evidence for the reliability of intestinal organoids as a patient-specific avatar. Breakthroughs now allow the generation of structurally and cellularly complex intestinal models to better capture a wider range of intestinal pathophysiology. As the field develops and evolves, there is a need for standardized frameworks for generation, culture, storage, and analysis of intestinal organoids to ensure reproducibility, comparability, and interpretability of these preclinical and clinical studies to ultimately enable clinical translation.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151474"},"PeriodicalIF":4.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909518","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}
引用次数: 0
Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries 内皮细胞Piezo1促进大动脉血管平滑肌细胞分化。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-20 DOI: 10.1016/j.ejcb.2024.151473
Javier Abello , Ying Yin , Yonghui Zhao , Josh Maurer , Jihui Lee , Cherokee Bodell , Jahmiera Richee , Abigail J. Clevenger , Zarek Burton , Megan E. Goeckel , Michelle Lin , Stephanie Grainger , Carmen M. Halabi , Shreya A. Raghavan , Rajan Sah , Amber N. Stratman
{"title":"Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries","authors":"Javier Abello ,&nbsp;Ying Yin ,&nbsp;Yonghui Zhao ,&nbsp;Josh Maurer ,&nbsp;Jihui Lee ,&nbsp;Cherokee Bodell ,&nbsp;Jahmiera Richee ,&nbsp;Abigail J. Clevenger ,&nbsp;Zarek Burton ,&nbsp;Megan E. Goeckel ,&nbsp;Michelle Lin ,&nbsp;Stephanie Grainger ,&nbsp;Carmen M. Halabi ,&nbsp;Shreya A. Raghavan ,&nbsp;Rajan Sah ,&nbsp;Amber N. Stratman","doi":"10.1016/j.ejcb.2024.151473","DOIUrl":"10.1016/j.ejcb.2024.151473","url":null,"abstract":"<div><div>Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating <em>klf2a,</em> a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed <em>klf2a</em> and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased <em>klf2a</em> levels and decreased vSMC association with arteries. We supported the small molecule findings with <em>in vivo</em> genetic suppression of <em>piezo1</em> and <em>2</em> in zebrafish, resulting in loss of <em>transgelin+</em> vSMCs on the dorsal aorta. Further, endothelial cell (EC)-specific <em>Piezo1</em> knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. To determine the underlying mechanism, we used <em>in vitro</em> modeling assays to demonstrate that differential sensing of pulsatile versus laminar flow forces across endothelial cells changes the expression of mural cell differentiation genes. Together, our findings suggest a crucial role for EC Piezo1 in sensing force within large arteries to mediate mural cell differentiation and stabilization of the arterial vasculature.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151473"},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893196","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}
引用次数: 0
Cholangiocyte organoids for disease, cancer, and regenerative medicine 胆管细胞类器官用于疾病、癌症和再生医学。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-19 DOI: 10.1016/j.ejcb.2024.151472
Munemasa Nagao , Akihisa Fukuda , Hirotaka Kashima , Sho Matsuyama , Kei Iimori , Shinnosuke Nakayama , Kenta Mizukoshi , Munenori Kawai , Go Yamakawa , Mayuki Omatsu , Mio Namikawa , Tomonori Masuda , Yukiko Hiramatsu , Yu Muta , Takahisa Maruno , Yuki Nakanishi , Tatsuaki Tsuruyama , Hiroshi Seno
{"title":"Cholangiocyte organoids for disease, cancer, and regenerative medicine","authors":"Munemasa Nagao ,&nbsp;Akihisa Fukuda ,&nbsp;Hirotaka Kashima ,&nbsp;Sho Matsuyama ,&nbsp;Kei Iimori ,&nbsp;Shinnosuke Nakayama ,&nbsp;Kenta Mizukoshi ,&nbsp;Munenori Kawai ,&nbsp;Go Yamakawa ,&nbsp;Mayuki Omatsu ,&nbsp;Mio Namikawa ,&nbsp;Tomonori Masuda ,&nbsp;Yukiko Hiramatsu ,&nbsp;Yu Muta ,&nbsp;Takahisa Maruno ,&nbsp;Yuki Nakanishi ,&nbsp;Tatsuaki Tsuruyama ,&nbsp;Hiroshi Seno","doi":"10.1016/j.ejcb.2024.151472","DOIUrl":"10.1016/j.ejcb.2024.151472","url":null,"abstract":"<div><div>The biliary tract is a ductal network comprising the intrahepatic (IHBDs) and extrahepatic bile duct (EHBDs). Biliary duct disorders include cholangitis, neoplasms, and injury. However, the underlying mechanisms are not fully understood. With advancements in 3D culture technology, cholangiocyte organoids (COs) derived from primary tissues or induced pluripotent stem cells (iPSCs) can accurately replicate the structural and functional properties of biliary tissues. These organoids have become powerful tools for studying the pathogenesis of biliary diseases, such as cystic fibrosis and primary sclerosing cholangitis, and for developing new therapeutic strategies for cholangiocarcinoma. Additionally, COs have the potential to repair bile duct injuries and facilitate transplantation therapies. This review also discusses the use of organoids in genetically engineered mouse models to provide mechanistic insights into tumorigenesis and cancer progression. Continued innovation and standardization of organoid technology are crucial for advancing precision medicine for biliary diseases and cancer.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151472"},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893191","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}
引用次数: 0
Beyond consciousness: Ethical, legal, and social issues in human brain organoid research and application 超越意识:人类大脑类器官研究和应用中的伦理、法律和社会问题。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-19 DOI: 10.1016/j.ejcb.2024.151470
Masanori Kataoka , Takuya Niikawa , Naoya Nagaishi , Tsung-Ling Lee , Alexandre Erler , Julian Savulescu , Tsutomu Sawai
{"title":"Beyond consciousness: Ethical, legal, and social issues in human brain organoid research and application","authors":"Masanori Kataoka ,&nbsp;Takuya Niikawa ,&nbsp;Naoya Nagaishi ,&nbsp;Tsung-Ling Lee ,&nbsp;Alexandre Erler ,&nbsp;Julian Savulescu ,&nbsp;Tsutomu Sawai","doi":"10.1016/j.ejcb.2024.151470","DOIUrl":"10.1016/j.ejcb.2024.151470","url":null,"abstract":"<div><div>This study aims to provide a comprehensive review of the ethical, legal and social issues in human brain organoid research, with a view to different types of research and applications: <em>in vitro</em> research, transplantation into non-human animals, and biocomputing. Despite the academic and societal attention on the possibility that human brain organoids may be conscious, we have identified diverse issues in human brain organoid research and applications. To guide the complex terrain of human brain organoid research and applications, a multidisciplinary approach that integrates ethical, legal, and social perspectives is essential.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151470"},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893231","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}
引用次数: 0
Phosphatidylserine on sperm head interact with Annexin A5 on oviduct luminal cilia to form a sperm reservoir in pigs 猪精子头部的磷脂酰丝氨酸与输卵管腔纤毛上的膜联蛋白A5相互作用,形成精子储存库。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-17 DOI: 10.1016/j.ejcb.2024.151471
Lorraine Schmaltz , Elie Barakat , Renaud Fleurot , Rustem Uzbekov , Karine Reynaud , Ludivine Laffont , Guillaume Tsikis , Isabelle Mérour , Pascal Mermillod , Marie Saint-Dizier
{"title":"Phosphatidylserine on sperm head interact with Annexin A5 on oviduct luminal cilia to form a sperm reservoir in pigs","authors":"Lorraine Schmaltz ,&nbsp;Elie Barakat ,&nbsp;Renaud Fleurot ,&nbsp;Rustem Uzbekov ,&nbsp;Karine Reynaud ,&nbsp;Ludivine Laffont ,&nbsp;Guillaume Tsikis ,&nbsp;Isabelle Mérour ,&nbsp;Pascal Mermillod ,&nbsp;Marie Saint-Dizier","doi":"10.1016/j.ejcb.2024.151471","DOIUrl":"10.1016/j.ejcb.2024.151471","url":null,"abstract":"<div><div>After insemination, a subpopulation of sperm reaches the oviducts and binds to isthmic epithelial cells to form a “sperm reservoir”. Our objective was to explore the role of annexin A5 (ANXA5), a protein that binds with high affinity to phosphatidylserine (PS), in the formation of the sperm reservoir in pigs.</div><div>Phosphatidylserine was detected on the head of approximately 10 % of boar sperm at ejaculation. Porcine ANXA5 was immunodetected with a strong signal on luminal cilia in the isthmus and in derived isthmic epithelial spheroids (IES). Exogenous PS between 0.01 and 0.1 µg/mL and recombinant porcine ANXA5 (rpANXA5) above 0.1 µg/mL inhibited sperm binding to IES without reducing sperm motility. Pre-incubation of sperm, but not IES, with rpANXA5 inhibited sperm binding to IES. Under capacitating conditions, the proportion of live sperm with head PS exposure and the ability of sperm to bind to rpANXA5 and IES cilia increased within 30 min. Conversely, the acrosome reaction decreased the ability of sperm to bind rpANXA5 and prevented sperm binding to IES.</div><div>In conclusion, sperm membrane remodelling during capacitation enhanced head PS exposure in motile sperm, resulting in increased interaction with ciliary ANXA5 on isthmic epithelial spheroids. These findings support a role for PS-ANXA5 interaction in the formation of the sperm reservoir in mammalian females.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151471"},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863752","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}
引用次数: 0
GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells GsMTx-4毒液毒素可拮抗人骨肉瘤细胞转移特性的生物物理调节。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-11 DOI: 10.1016/j.ejcb.2024.151469
Arianna Buglione , Giulia Alloisio , Chiara Ciaccio , David Becerril Rodriguez , Simone Dogali , Marco Luce , Stefano Marini , Antonio Cricenti , Magda Gioia
{"title":"GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells","authors":"Arianna Buglione ,&nbsp;Giulia Alloisio ,&nbsp;Chiara Ciaccio ,&nbsp;David Becerril Rodriguez ,&nbsp;Simone Dogali ,&nbsp;Marco Luce ,&nbsp;Stefano Marini ,&nbsp;Antonio Cricenti ,&nbsp;Magda Gioia","doi":"10.1016/j.ejcb.2024.151469","DOIUrl":"10.1016/j.ejcb.2024.151469","url":null,"abstract":"<div><div>Despite their genetic diversity, metastatic cells converge on similar physical constraints during tumor progression. At the nanoscale, these forces can induce substantial molecular deformations, altering the structure and behavior of cancer cells. To address the challenges of osteosarcoma (OS), a highly aggressive cancer, we explored the mechanobiology of OS cells, <em>in vitro</em>. Using uniaxial-stretching technology, we examined the biophysical modulation of metastatic traits in SAOS-2, U-2 OS, and non-tumorigenic hFOB cells. Changes in cell morphology were quantified using confocal and fluorescence microscopy. To elucidate the molecular mechanisms that translate biomechanical alterations into biochemical responses, we employed Western blotting, real-time quantitative RT-PCR, reactive oxygen species ROS assay, and the mechanosensitive channel blocker Grammostola MechanoToxin4 (GsMTx-4). Our study reveals that mechanical stimulation uniquely affects OS cells, increasing nuclear size and altering the N/C ratio. We found that mechanosensitive (MS) channels are activated, leading to ROS accumulation, Src protein modulation, and histone H3 acetylation. These changes influence OS cell motility and adhesion but not proliferation. Importantly, mechanical preconditioning differentially impacts doxorubicin resistance, correlating with the Src-H3 acetylation axis. This study underscores the critical role of MS channels in OS cells and highlights the importance of mechanobiology in identifying molecular pathways that traditional biochemical approaches may not reveal. Notably, the GsMTx-4 venom peptide effectively countered mechanically induced responses, particularly by inhibiting OS cell migration, without harming healthy cells. Thus, suggesting its potential as a promising therapeutic agent for targeting osteosarcoma metastasis</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"104 1","pages":"Article 151469"},"PeriodicalIF":4.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822017","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}
引用次数: 0
Editorial overview: EJCB Special Issue – Cell host-pathogen interactions 编辑综述:EJCB 特刊--细胞宿主与病原体之间的相互作用。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-12-01 DOI: 10.1016/j.ejcb.2024.151462
Serge Mostowy , Theresia E.B. Stradal
{"title":"Editorial overview: EJCB Special Issue – Cell host-pathogen interactions","authors":"Serge Mostowy ,&nbsp;Theresia E.B. Stradal","doi":"10.1016/j.ejcb.2024.151462","DOIUrl":"10.1016/j.ejcb.2024.151462","url":null,"abstract":"","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151462"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497505","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}
引用次数: 0
Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression 小细胞肺癌进展过程中的 mTOR 活性和 RICTOR 拷贝数增加。
IF 4.5 3区 生物学
European journal of cell biology Pub Date : 2024-11-19 DOI: 10.1016/j.ejcb.2024.151468
Dániel Sztankovics , Fatime Szalai , Dorottya Moldvai , Titanilla Dankó , Noémi Nagy , Judit Pápay , András Khoór , Ildikó Krencz , Anna Sebestyén
{"title":"Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression","authors":"Dániel Sztankovics ,&nbsp;Fatime Szalai ,&nbsp;Dorottya Moldvai ,&nbsp;Titanilla Dankó ,&nbsp;Noémi Nagy ,&nbsp;Judit Pápay ,&nbsp;András Khoór ,&nbsp;Ildikó Krencz ,&nbsp;Anna Sebestyén","doi":"10.1016/j.ejcb.2024.151468","DOIUrl":"10.1016/j.ejcb.2024.151468","url":null,"abstract":"<div><div>Small cell lung carcinoma (SCLC) is a highly malignant cancer with early metastatic dissemination and poor clinical outcomes. Mutations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, including the frequently occurring rapamycin-insensitive protein (<em>RICTOR</em>) amplification, have been described in these tumours. Moreover, the associated mTOR hyperactivity could be exploited for personalised treatment. Our aim was to study mTOR activity, <em>RICTOR</em> amplification, and their role during SCLC progression. <em>In situ</em> mTOR activity and Rictor expression were characterised by immunohistochemistry in 50 primary and 50 brain metastatic tumours, and 14 paired SCLC patient samples. <em>RICTOR</em> copy number changes were analysed by fluorescence <em>in situ</em> hybridisation of the paired SCLC patient samples and <em>in vivo</em> experiments. Additionally, <em>in vitro</em> sensitivity to cisplatin and mTOR inhibitors was evaluated in SCLC cell lines harbouring <em>RICTOR</em> amplification and other mTOR pathway mutations. High Rictor expression and mTOR complex 2 (mTORC2) hyperactivity were significantly associated with brain metastases and worse overall survival. An increase in <em>RICTOR</em> copy number was observed in paired samples during progression. The importance of these alterations was confirmed both by the sensitising effect of vistusertib <em>in vitro</em> and the <em>RICTOR</em> copy number/expression changes in xenografts. Our study highlights the role of mTORC2 in SCLC progression. Early detection of <em>RICTOR</em> amplification in primary tumours and targeting mTORC2 in these cases may represent a promising novel strategy to develop personalised therapy for metastasis prevention.</div></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 4","pages":"Article 151468"},"PeriodicalIF":4.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686320","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}
引用次数: 0
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