Life Science Alliance最新文献_第3页

Endolysosome-targeted nanoparticle delivery of antiviral therapy for coronavirus infections. 内溶酶体靶向纳米颗粒递送冠状病毒感染抗病毒治疗。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-03 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403182

Anton Petcherski, Brett M Tingley, Andrew Martin, Sarah Adams, Alexandra J Brownstein, Ross A Steinberg, Byourak Shabane, Jennifer Ngo, Corey Osto, Gustavo Garcia, Michaela Veliova, Vaithilingaraja Arumugaswami, Aaron H Colby, Orian S Shirihai, Mark W Grinstaff

{"title":"Endolysosome-targeted nanoparticle delivery of antiviral therapy for coronavirus infections.","authors":"Anton Petcherski, Brett M Tingley, Andrew Martin, Sarah Adams, Alexandra J Brownstein, Ross A Steinberg, Byourak Shabane, Jennifer Ngo, Corey Osto, Gustavo Garcia, Michaela Veliova, Vaithilingaraja Arumugaswami, Aaron H Colby, Orian S Shirihai, Mark W Grinstaff","doi":"10.26508/lsa.202403182","DOIUrl":"10.26508/lsa.202403182","url":null,"abstract":"SARS-CoV-2 can infect cells through endocytic uptake, a process that is targeted by inhibition of lysosomal proteases. However, clinically this approach to treat viral infections has afforded mixed results, with some studies detailing an oral regimen of hydroxychloroquine accompanied by significant off-target toxicities. We rationalized that an organelle-targeted approach will avoid toxicity while increasing the concentration of the drug at the target. Here, we describe a lysosome-targeted, mefloquine-loaded poly(glycerol monostearate-co-ε-caprolactone) nanoparticle (MFQ-NP) for pulmonary delivery via inhalation. Mefloquine is a more effective inhibitor of viral endocytosis than hydroxychloroquine in cellular models of COVID-19. MFQ-NPs are less toxic than molecular mefloquine, are 100-150 nm in diameter, and possess a negative surface charge, which facilitates uptake via endocytosis allowing inhibition of lysosomal proteases. MFQ-NPs inhibit coronavirus infection in mouse MHV-A59 and human OC43 coronavirus model systems and inhibit SARS-CoV-2 WA1 and its Omicron variant in a human lung epithelium model. Organelle-targeted delivery is an effective means to inhibit viral infection.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123200","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

Cholesterol ensures ciliary polycystin-2 localization to prevent polycystic kidney disease. 胆固醇可确保纤毛多囊蛋白-2定位，从而预防多囊肾病。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-02-03 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403063

Takeshi Itabashi, Kosuke Hosoba, Tomoka Morita, Sotai Kimura, Kenji Yamaoka, Moe Hirosawa, Daigo Kobayashi, Hiroko Kishi, Kodai Kume, Hiroshi Itoh, Hideshi Kawakami, Kouichi Hashimoto, Takashi Yamamoto, Tatsuo Miyamoto

{"title":"Cholesterol ensures ciliary polycystin-2 localization to prevent polycystic kidney disease.","authors":"Takeshi Itabashi, Kosuke Hosoba, Tomoka Morita, Sotai Kimura, Kenji Yamaoka, Moe Hirosawa, Daigo Kobayashi, Hiroko Kishi, Kodai Kume, Hiroshi Itoh, Hideshi Kawakami, Kouichi Hashimoto, Takashi Yamamoto, Tatsuo Miyamoto","doi":"10.26508/lsa.202403063","DOIUrl":"10.26508/lsa.202403063","url":null,"abstract":"The plasma membrane covering the primary cilium has a diverse accumulation of receptors and channels. To ensure the sensor function of the cilia, the ciliary membrane has higher cholesterol content than other cell membrane regions. A peroxisomal biogenesis disorder, Zellweger syndrome, characterized by polycystic kidney, is associated with a reduced level of ciliary cholesterol in cells. However, the etiological mechanism by which ciliary cholesterol lowering causes polycystic kidney disease remains unclear. Here, we demonstrated that lowering ciliary cholesterol by either pharmacological treatment or genetic depletion of peroxisomes impairs the localization of a ciliary ion channel polycystin-2. We also generated cultured renal medullary cells and mice carrying a missense variant in the cholesterol-binding site of polycystin-2 detected in the patient database of autosomal dominant polycystic kidney disease. This missense protein showed normal channel activity but decreased localization to the ciliary membrane. The homozygous mice exhibited embryonic lethality and the ciliopathy spectrum conditions of situs inversus and polycystic kidney. Our results suggest that cholesterol controls the ciliary localization of polycystin-2 to prevent polycystic kidney disease.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123199","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

Cryo-EM structures reveal the H⁺/citrate symport mechanism of Drosophila INDY. 低温电镜结构揭示了果蝇INDY的H+/柠檬酸同调机制。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-30 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402992

Subin Kim, Jun Gyou Park, Seung Hun Choi, Ji Won Kim, Mi Sun Jin

引用次数: 0

Human genetic variants in SLC39A8 impact uptake and steady-state metal levels within the cell. SLC39A8的人类遗传变异影响细胞内的摄取和稳态金属水平。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-30 Print Date: 2025-04-01 DOI: 10.26508/lsa.202403028

Wen-An Wang, Andrea Garofoli, Evandro Ferrada, Christoph Klimek, Barbara Steurer, Alvaro Ingles-Prieto, Tanja Osthushenrich, Aidan MacNamara, Anders Malarstig, Tabea Wiedmer, Giulio Superti-Furga

{"title":"Human genetic variants in SLC39A8 impact uptake and steady-state metal levels within the cell.","authors":"Wen-An Wang, Andrea Garofoli, Evandro Ferrada, Christoph Klimek, Barbara Steurer, Alvaro Ingles-Prieto, Tanja Osthushenrich, Aidan MacNamara, Anders Malarstig, Tabea Wiedmer, Giulio Superti-Furga","doi":"10.26508/lsa.202403028","DOIUrl":"10.26508/lsa.202403028","url":null,"abstract":"The human SLC39A8 (hSLC39A8) gene encodes a plasma membrane protein SLC39A8 (ZIP8) that mediates the specific uptake of the metals Cd2+, Mn2+, Zn2+, Fe2+, Co2+, and Se4+ Pathogenic variants within hSLC39A8 are associated with congenital disorder of glycosylation type 2 (CDG type II) or Leigh-like syndrome. However, numerous mutations of uncertain significance are also linked to different conditions or benign traits. Our study characterized 21 hSLC39A8 variants and measured their impact on protein localization and intracellular levels of Cd2+, Zn2+, and Mn2+ We identified four variants that disrupt protein expression, five variants with high retention in the endoplasmic reticulum, and 12 variants with localization to the plasma membrane. From the 12 variants with plasma membrane localization, we identified three with complete loss of detectable ion uptake by the cell and five with differential uptake between metal ions. Further in silico analysis on protein stability identified variants that may affect the stability of homodimer interfaces. This study elucidates the variety of effects of hSLC39A8 variants on ZIP8 and on diseases involving disrupted metal ion homeostasis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066533","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

A role for mitochondria-ER crosstalk in amyotrophic lateral sclerosis 8 pathogenesis. 线粒体-内质网串扰在肌萎缩性侧索硬化发病中的作用。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-27 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402907

Cathal Wilson, Laura Giaquinto, Michele Santoro, Giuseppe Di Tullio, Valentina Morra, Wanda Kukulski, Rossella Venditti, Francesca Navone, Nica Borgese, Maria Antonietta De Matteis

{"title":"A role for mitochondria-ER crosstalk in amyotrophic lateral sclerosis 8 pathogenesis.","authors":"Cathal Wilson, Laura Giaquinto, Michele Santoro, Giuseppe Di Tullio, Valentina Morra, Wanda Kukulski, Rossella Venditti, Francesca Navone, Nica Borgese, Maria Antonietta De Matteis","doi":"10.26508/lsa.202402907","DOIUrl":"10.26508/lsa.202402907","url":null,"abstract":"Protein aggregates in motoneurons, a pathological hallmark of amyotrophic lateral sclerosis, have been suggested to play a key pathogenetic role. ALS8, characterized by ER-associated inclusions, is caused by a heterozygous mutation in VAPB, which acts at multiple membrane contact sites between the ER and almost all other organelles. The link between protein aggregation and cellular dysfunction is unclear. A yeast model, expressing human mutant and WT-VAPB under the control of the orthologous yeast promoter in haploid and diploid cells, was developed to mimic the disease situation. Inclusion formation was found to be a developmentally regulated process linked to mitochondrial damage that could be attenuated by reducing ER-mitochondrial contacts. The co-expression of the WT protein retarded P56S-VAPB inclusion formation. Importantly, we validated these results in mammalian motoneuron cells. Our findings indicate that (age-related) damage to mitochondria influences the propensity of the mutant VAPB to form aggregates via ER-mitochondrial contacts, initiating a series of events leading to disease progression.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052953","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

Gastric cancer genomics study using reference human pangenomes. 利用人类泛基因组进行胃癌基因组学研究。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-27 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402977

Du Jiao, Xiaorui Dong, Shiyu Fan, Xinyi Liu, Yingyan Yu, Chaochun Wei

{"title":"Gastric cancer genomics study using reference human pangenomes.","authors":"Du Jiao, Xiaorui Dong, Shiyu Fan, Xinyi Liu, Yingyan Yu, Chaochun Wei","doi":"10.26508/lsa.202402977","DOIUrl":"10.26508/lsa.202402977","url":null,"abstract":"A pangenome is the sum of the genetic information of all individuals in a species or a population. Genomics research has been gradually shifted to a paradigm using a pangenome as the reference. However, in disease genomics study, pangenome-based analysis is still in its infancy. In this study, we introduced a graph-based pangenome GGCPan from 185 patients with gastric cancer. We then systematically compared the cancer genomics study results using GGCPan, a linear pangenome GCPan, and the human reference genome as the reference. For small variant detection and microsatellite instability status identification, there is little difference in using three different genomes. Using GGCPan as the reference had a significant advantage in structural variant identification. A total of 24 candidate gastric cancer driver genes were detected using three different reference genomes, of which eight were common and five were detected only based on pangenomes. Our results showed that disease-specific pangenome as a reference is promising and a whole set of tools are still to be developed or improved for disease genomics study in the pangenome era.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052956","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

High-resolution analysis of human centromeric chromatin. 人类着丝粒染色质的高分辨率分析。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-23 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402819

Daniël P Melters, Minh Bui, Tatini Rakshit, Sergei A Grigoryev, David Sturgill, Yamini Dalal

{"title":"High-resolution analysis of human centromeric chromatin.","authors":"Daniël P Melters, Minh Bui, Tatini Rakshit, Sergei A Grigoryev, David Sturgill, Yamini Dalal","doi":"10.26508/lsa.202402819","DOIUrl":"10.26508/lsa.202402819","url":null,"abstract":"Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays. CENP-C complex-bound chromatin was refractory to MNase digestion. The CENP-C complex increased in height throughout the cell cycle culminating in mitosis, and the smaller CENP-C complex corresponds to the dimensions of in vitro reconstituted constitutive centromere-associated network. In addition, we found two distinct CENP-A nucleosomal configurations; the taller variant was associated with the CENP-C complex. Finally, CENP-A mutants partially corrected CENP-C overexpression-induced centromeric transcription and mitotic defects. In all, our data support a working model in which CENP-C is critical in regulating centromere homeostasis by supporting a unique higher order structure of centromeric chromatin and altering the accessibility of the centromeric chromatin fiber for transcriptional machinery.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029135","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

NME7 maintains primary cilium assembly, ciliary microtubule stability, and Hedgehog signaling. NME7维持初级纤毛组装、纤毛微管稳定性和Hedgehog信号传导。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-17 Print Date: 2025-04-01 DOI: 10.26508/lsa.202402933

Menghui Ji, Wenjuan Cui, Qian Feng, Jingjin Qi, Xinmin Wang, Hong Zhu, Wenqing Zhang, Wenxiang Fu

{"title":"NME7 maintains primary cilium assembly, ciliary microtubule stability, and Hedgehog signaling.","authors":"Menghui Ji, Wenjuan Cui, Qian Feng, Jingjin Qi, Xinmin Wang, Hong Zhu, Wenqing Zhang, Wenxiang Fu","doi":"10.26508/lsa.202402933","DOIUrl":"10.26508/lsa.202402933","url":null,"abstract":"NME7 (nucleoside diphosphate kinase 7), a lesser studied member of the non-metastatic expressed (NME) family, has been reported as a potential subunit of the γ-tubulin ring complex (γTuRC). However, its role in the cilium assembly and function remains unclear. Our research demonstrated that NME7 is located at the centrosome, including at the spindle poles during metaphase and at the basal bodies during cilium assembly. Notably, a small fraction of NME7 localizes within the cilium. Detailed analysis of cilium assembly after NME7 knockdown and knockout revealed that NME7 is required for this process. NME7 knockout cells exhibited sensitivity to nocodazole, indicating its role in ciliary microtubule stability. In addition, NME7 deficiency impacted the Hedgehog signaling pathway, evident from reduced smoothened (Smo) fluorescence within primary cilia. This role of NME7 in Hedgehog signaling may depend on its nucleoside diphosphate kinase activity and γTuRC association. In conclusion, these findings enhance our understanding of the γTuRC roles in primary cilia in mammalian cells, highlighting the importance of NME7 in ciliary functions and signaling pathways.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007970","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

Trans-scale live-imaging of an E5.5 mouse embryo using incubator-type biaxial light-sheet microscopy. 利用培养型双轴光片显微镜对E5.5小鼠胚胎进行跨尺度实时成像。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-15 Print Date: 2025-03-01 DOI: 10.26508/lsa.202402839

Go Shioi, Tomonobu M Watanabe, Junichi Kaneshiro, Yusuke Azuma, Shuichi Onami

{"title":"Trans-scale live-imaging of an E5.5 mouse embryo using incubator-type biaxial light-sheet microscopy.","authors":"Go Shioi, Tomonobu M Watanabe, Junichi Kaneshiro, Yusuke Azuma, Shuichi Onami","doi":"10.26508/lsa.202402839","DOIUrl":"10.26508/lsa.202402839","url":null,"abstract":"During mouse embryonic development, the embryonic day (E) 5.5 stage represents a crucial period for the formation of the primitive body axis, where the symmetry breaking of cellular states influences the multicellular system. Elucidating the detailed mechanisms of this process necessitates a trans-layered dynamic observation of the embryo and all internal cells. In this report, we present our success in achieving in-toto single-cell observation in a whole hemisphere of an E5.5 embryo for 12 h, using a newly developed incubator-type biaxial light-sheet microscope. To achieve the success, we optimized our microscope system, including an incubator for culture stability, and refining the observation protocol to reduce phototoxicity. Our key discovery is that the scan speed during light-sheet formation plays a critical role in reducing phototoxicity, rather than the irradiation intensity or the interval time between frames. This innovative system not only enabled in-toto single-cell tracking but also led to the discovery of the abrupt shrinking of embryos whose contractile center was located at the extraembryonic ectoderm during monotonous growth up to the E6.5 stage.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007968","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

Transcription factor EB (TFEB) activity increases resistance of TNBC stem cells to metabolic stress. 转录因子EB （TFEB）活性增加TNBC干细胞对代谢应激的抗性。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2025-01-15 Print Date: 2025-03-01 DOI: 10.26508/lsa.202302259

Milad Soleimani, Mark Duchow, Ria Goyal, Alexander Somma, Tamer S Kaoud, Kevin N Dalby, Jeanne Kowalski, S Gail Eckhardt, Carla Van Den Berg

{"title":"Transcription factor EB (TFEB) activity increases resistance of TNBC stem cells to metabolic stress.","authors":"Milad Soleimani, Mark Duchow, Ria Goyal, Alexander Somma, Tamer S Kaoud, Kevin N Dalby, Jeanne Kowalski, S Gail Eckhardt, Carla Van Den Berg","doi":"10.26508/lsa.202302259","DOIUrl":"10.26508/lsa.202302259","url":null,"abstract":"Breast cancer stem cells (CSCs) are difficult to therapeutically target, but continued efforts are critical given their contribution to tumor heterogeneity and treatment resistance in triple-negative breast cancer. CSC properties are influenced by metabolic stress, but specific mechanisms are lacking for effective drug intervention. Our previous work on TFEB suggested a key function in CSC metabolism. Indeed, TFEB knockdown (KD) inhibited mammosphere formation in vitro and tumor initiation/growth in vivo. These phenotypic effects were accompanied by a decline in CD44high/CD24low cells. Glycolysis inhibitor 2-deoxy-D-glucose (2-DG) induced TFEB nuclear translocation, indicative of TFEB transcriptional activity. TFEB KD blunted, whereas TFEB (S142A) augmented 2-DG-driven unfolded protein response (UPR) mediators, notably BiP/HSPA5 and CHOP. Like TFEB KD, silencing BiP/HSPA5 inhibited CSC self-renewal, suggesting that TFEB augments UPR-related survival. Further studies showed that TFEB KD attenuated 2-DG-directed autophagy, suggesting a mechanism whereby TFEB protects CSCs against 2-DG-induced stress. Our data indicate that TFEB modulates CSC metabolic stress response via autophagy and UPR. These findings reveal the novel role of TFEB in regulating CSCs during metabolic stress in triple-negative breast cancer.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007967","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