Journal of Molecular Cell Biology最新文献_第7页

Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression. Temsirolimus 可抑制 FSP1 酶的活性，从而诱导铁变态反应，抑制肝癌的进展。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae036

Rui-Lin Tian, Tian-Xiang Wang, Zi-Xuan Huang, Zhen Yang, Kun-Liang Guan, Yue Xiong, Pu Wang, Dan Ye

{"title":"Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression.","authors":"Rui-Lin Tian, Tian-Xiang Wang, Zi-Xuan Huang, Zhen Yang, Kun-Liang Guan, Yue Xiong, Pu Wang, Dan Ye","doi":"10.1093/jmcb/mjae036","DOIUrl":"10.1093/jmcb/mjae036","url":null,"abstract":"Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent accumulation of lipid peroxidation. While lipid radical elimination reaction catalyzed by glutathione peroxidase 4 (GPX4) is a major anti-ferroptosis mechanism, inhibiting this pathway pharmaceutically shows promise as an antitumor strategy. However, certain tumor cells exhibit redundancy in lipid radical elimination pathways, rendering them unresponsive to GPX4 inhibitors. In this study, we conducted screens across different cancer cell lines and Food and Drug Administration-approved drugs, leading to the identification of temsirolimus in combination with the GPX4 inhibitor RSL3 as a potent inducer of ferroptosis in liver cancer cells. Mechanistically, temsirolimus sensitized liver cancer cells to ferroptosis by directly binding to and inhibiting ferroptosis suppressor protein 1 (FSP1) enzyme. Notably, while temsirolimus is recognized as a potent mammalian target of rapamycin (mTOR) inhibitor, its ferroptosis-inducing effect is primarily attributed to the inhibition of FSP1 rather than mTOR activity. By employing in vitro colony formation assays and in vivo tumor xenograft models, we demonstrated that the combination of temsirolimus and RSL3 effectively suppressed liver tumor progression. This tumoricidal effect was associated with increased lipid peroxidation and induction of ferroptosis. In conclusion, our findings underscore the potential of combining multitarget ferroptosis-inducing agents to circumvent the resistance to ferroptosis of liver cancer cells and highlight temsirolimus as a promising FSP1 inhibitor and ferroptosis inducer, which also deserves further investigation in translational medicine.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Correction to: Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy. 更正为线粒体醛脱氢酶通过 GSK3β 介导的线粒体完整性保护和 Parkin 介导的有丝分裂，拯救糖尿病心肌病。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae032

引用次数: 0

ATP promotes protein coacervation through conformational compaction. ATP 通过构象压实促进蛋白质共轭。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae038

Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong

{"title":"ATP promotes protein coacervation through conformational compaction.","authors":"Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong","doi":"10.1093/jmcb/mjae038","DOIUrl":"10.1093/jmcb/mjae038","url":null,"abstract":"Adenosine triphosphate (ATP) has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered Arg-Gly/Arg-Gly-Gly (RG/RGG) rich motif from the HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that, at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs and accounts for the distinct phase separation behaviors of the charge-rich RGG motif and other low-complexity IDPs.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Hypoxia signaling in the adipose tissue. 脂肪组织中的缺氧信号传导

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae039

Phu M Huynh, Fenfen Wang, Yu A An

引用次数: 0

Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine. 利用亚硝基胍在三维有机体中模拟胃肠化生。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-12-20 DOI: 10.1093/jmcb/mjae030

Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding

{"title":"Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.","authors":"Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding","doi":"10.1093/jmcb/mjae030","DOIUrl":"10.1093/jmcb/mjae030","url":null,"abstract":"Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

ZW10: an emerging orchestrator of organelle dynamics during the cell division cycle. ZW10：细胞分裂周期中细胞器动力学的新兴协调者

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-12-20 DOI: 10.1093/jmcb/mjae026

Sm Faysal Bellah, Fengrui Yang, Fangyuan Xiong, Zhen Dou, Xuebiao Yao, Xing Liu

引用次数: 0

Sterile activation of RNA-sensing pathways in autoimmunity. 无菌激活自身免疫中的 RNA 传感途径

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-12-20 DOI: 10.1093/jmcb/mjae029

Jiaxin Li, Junyan Zhu, Hui Yang, Fajian Hou

引用次数: 0

PHLDA2 is critical for p53-mediated ferroptosis and tumor suppression. PHLDA2 对 p53 介导的铁变态反应和肿瘤抑制至关重要。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-12-20 DOI: 10.1093/jmcb/mjae033

Xin Yang, Wei Gu

引用次数: 0

Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis. 人类淋巴造血过程中替代多腺苷酸化的单细胞图谱。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-12-20 DOI: 10.1093/jmcb/mjae027

Jiaqi Qiang, Shan Yu, Jun Li, Yu Rong, Xiaoshuang Wang, Yong Zhu, Fang Wang

{"title":"Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis.","authors":"Jiaqi Qiang, Shan Yu, Jun Li, Yu Rong, Xiaoshuang Wang, Yong Zhu, Fang Wang","doi":"10.1093/jmcb/mjae027","DOIUrl":"10.1093/jmcb/mjae027","url":null,"abstract":"Alternative polyadenylation (APA) is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites (PASs). APA is involved in lymphocyte activation; however, its role throughout the entire differentiation trajectory remains elusive. Here, we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells (HSPCs) to terminally differentiated lymphocytes. This analysis covered 19973 cells of 12 clusters from five lineages (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, and plasmacytoid dendritic cells). A total of 2364 genes exhibited differential 3'-untranslated region (3'UTR) PAS usage, and 3021 genes displayed differential intronic cleavage during lymphoid differentiation. We observed a global trend of 3'UTR shortening during lymphoid differentiation. Nevertheless, specific events of both 3'UTR shortening and lengthening were also identified within each cluster. The APA patterns delineated three differentiation stages: HSPCs, precursor cells, and mature cells. Moreover, we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes (TCF7 and NFATC2IP), immune function-related genes (BCL2, CD5, CD28, GOLT1B, and TMEM59), and protein ubiquitination-related genes (UBE2G1, YPEL5, and SUMO3). These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Blockade of TNF-α/TNFR2 signalling suppresses colorectal cancer and enhances the efficacy of anti-PD1 immunotherapy by decreasing CCR8+T regulatory cells. 阻断TNF-α/TNFR2信号抑制结直肠癌癌症，并通过减少CCR8+T调节细胞来增强抗PD1免疫疗法的疗效。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-11-25 DOI: 10.1093/jmcb/mjad067

Yixian Guo, Feng Xie, Xu Liu, Shouyu Ke, Jieqiong Chen, Yi Zhao, Ning Li, Zeyu Wang, Gang Yi, Yanying Shen, Dan Li, Chunchao Zhu, Zizhen Zhang, Gang Zhao, Hong Lu, Bin Li, Wenyi Zhao

{"title":"Blockade of TNF-α/TNFR2 signalling suppresses colorectal cancer and enhances the efficacy of anti-PD1 immunotherapy by decreasing CCR8+T regulatory cells.","authors":"Yixian Guo, Feng Xie, Xu Liu, Shouyu Ke, Jieqiong Chen, Yi Zhao, Ning Li, Zeyu Wang, Gang Yi, Yanying Shen, Dan Li, Chunchao Zhu, Zizhen Zhang, Gang Zhao, Hong Lu, Bin Li, Wenyi Zhao","doi":"10.1093/jmcb/mjad067","DOIUrl":"10.1093/jmcb/mjad067","url":null,"abstract":"The enrichment of regulatory T cells (Tregs) in the tumour microenvironment (TME) has been recognized as one of the major factors in the initiation and development of resistance to immune checkpoint inhibitors. C-C motif chemokine receptor 8 (CCR8), a marker of activated suppressive Tregs, has a significant impact on the functions of Tregs in the TME. However, the regulatory mechanism of CCR8 in Tregs remains unclear. Here, we revealed that a high level of TNF-α in the colorectal cancer (CRC) microenvironment upregulated CCR8 expression in Tregs via the TNFR2/NF-κB signalling pathway and the FOXP3 transcription factor. Furthermore, in both anti-programmed cell death protein 1 (anti-PD1)-responsive and anti-PD1-unresponsive tumour models, PD1 blockade induced CCR8+ Treg infiltration. In both models, Tnfr2 depletion or TNFR2 blockade suppressed tumour progression by reducing CCR8+ Treg infiltration and thus augmented the efficacy of anti-PD1 therapy. Finally, we identified that TNFR2+CCR8+ Tregs but not total Tregs were positively correlated with adverse prognosis in patients with CRC and gastric cancer. Our work reveals the regulatory mechanisms of CCR8 in Tregs and identifies TNFR2 as a promising target for immunotherapy.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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