IF 4.1

Cell Stress Pub Date : 2024-08-09 eCollection Date: 2024-01-01 DOI: 10.15698/cst2024.08.298

Mantas Silkunas, Olga N Pakhomova, Giedre Silkuniene, Andrei G Pakhomov

{"title":"Dynamics of cell membrane lesions and adaptive conductance under the electrical stress.","authors":"Mantas Silkunas, Olga N Pakhomova, Giedre Silkuniene, Andrei G Pakhomov","doi":"10.15698/cst2024.08.298","DOIUrl":"10.15698/cst2024.08.298","url":null,"abstract":"Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca2+ entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a low 50- to 300-pS conductance, which disappeared instantly once the hyperpolarization was removed. Charging to -240 mV created high-conductance (> 1 nS) pores which persisted for seconds even at zero membrane potential. With incremental hyperpolarization steps, persistent pores often emerged at locations different from those where the short-lived, low-conductance pores or diffuse permeabilization were previously observed. Attempts to polarize membrane beyond the threshold for the formation of persistent pores increased their conductance adaptively, preventing further potential build-up and \"clamping\" it at a certain limit (-270 ± 6 mV in HEK cells, -284 ± 5 mV in CHO cells, and -243 ± 9 mV in neurons). The data suggest a previously unknown role of electroporative lesions as a protective mechanism against a potentially fatal membrane overcharging and cell disintegration.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment. 唾液，人体的分子反映？对诊断和治疗的意义。

IF 6.4

Cell Stress Pub Date : 2024-05-27 eCollection Date: 2024-01-01 DOI: 10.15698/cst2024.05.297

Vincent Géli, Norbert Nabet

引用次数: 0

CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis? CircRNA调控ATG4B的液-液相分离，这是一种抑制癌症转移的新策略？

IF 4.1

Cell Stress Pub Date : 2024-05-24 eCollection Date: 2024-01-01 DOI: 10.15698/cst2024.05.296

Ziyuan Guo, Yang Chen, Yaran Wu, Jiqin Lian

{"title":"CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis?","authors":"Ziyuan Guo, Yang Chen, Yaran Wu, Jiqin Lian","doi":"10.15698/cst2024.05.296","DOIUrl":"10.15698/cst2024.05.296","url":null,"abstract":"Anoikis is a common programmed death for most of detached cells, but cancer cells can obtain anoikis resistance to facilitate their distant metastasis through the circulation system. Researches have indicated that enhanced autophagic flux accounts for the survival of many cancer cells under detached conditions. Targeting ATG4B, the key factor of autophagy progress, can inhibit cancer metastasis in vitro, but ATG4B-deficient mice are susceptible to many serious diseases, which indicates the potential uncontrolled side effects of direct targeting of ATG4B. In our recent research, we confirmed that ATG4B is a novel RNA binding protein in the gastric cancer (GC) cell. It interacts with circSPECC1 which consequently facilitates the liquid-liquid phase separation and ubiquitination of ATG4B. Additionally, the m6A reader ELAVL1 inhibits the expression of circSPECC1 to enhance the expression of ATG4B and anoikis resistance of GC cells. Further, we screened out an FDA-approved compound, lopinavir, to restore circSPECC1 abundance and suppress GC metastasis. In conclusion, our research identified a novel signal pathway (ELAVL1-circSPECC1-ATG4B-autophagy) to facilitate anoikis resistance and metastasis of GC cells and screened out a compound with clinical application potential to block this pathway, providing a novel strategy for the prevention of GC metastasis.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome. 在哈钦森-吉尔福特早衰综合征中，细胞质 EP300 对 mTORC1 的致病性过度激活。

IF 6.4

Cell Stress Pub Date : 2024-04-30 eCollection Date: 2024-01-01 DOI: 10.15698/cst2024.04.295

Lucille Ferret, Guido Kroemer, Mojgan Djavaheri-Mergny

引用次数: 0

The missing hallmark of health: psychosocial adaptation. 缺失的健康标志：社会心理适应。

IF 6.4

Cell Stress Pub Date : 2024-03-12 eCollection Date: 2024-01-01 DOI: 10.15698/cst2024.03.294

Carlos López-Otín, Guido Kroemer

引用次数: 0

MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression. MiR-200c 可重塑成纤维细胞，使其重现乳腺癌进展过程中 CAF 的表型。

IF 6.4

Cell Stress Pub Date : 2024-03-11 eCollection Date: 2024-01-01 DOI: 10.15698/cst2024.03.293

Zhao Lin, Megan E Roche, Víctor Díaz-Barros, Marina Domingo-Vidal, Diana Whitaker-Menezes, Madalina Tuluc, Guldeep Uppal, Jaime Caro, Joseph M Curry, Ubaldo Martinez-Outschoorn

{"title":"MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression.","authors":"Zhao Lin, Megan E Roche, Víctor Díaz-Barros, Marina Domingo-Vidal, Diana Whitaker-Menezes, Madalina Tuluc, Guldeep Uppal, Jaime Caro, Joseph M Curry, Ubaldo Martinez-Outschoorn","doi":"10.15698/cst2024.03.293","DOIUrl":"10.15698/cst2024.03.293","url":null,"abstract":"Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma cell resistance to apoptosis, proliferation and immunosuppression, leading to primary tumor growth, metastases, and resistance to immuno-chemotherapy. Conversely, miR-200c inhibition in fibroblasts restrains tumor growth with abated oxidative stress and an anti-tumorigenic immune environment. This work determines the mechanisms by which MET in CAFs via miR-200c transcriptional enrichment with DNA demethylation triggered by oxidative stress promotes cancer progression. CAFs undergoing MET trans-differentiation and senescence coordinate heterotypic signaling that may be targeted as an anti-cancer strategy.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10927306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 versatile method for the identification of senolytic compounds 鉴定衰老化合物的多功能方法

IF 6.4

Cell Stress Pub Date : 2023-12-01 DOI: 10.15698/cst2023.12.292

Chiara Annunziata, Francesca Castoldi, Jan Schlegel, Hazel X. Ang, Mina Ristovska, Stefania Melini, Robert Welch, Christian G. Riedel, Federico Pietrocola

{"title":"A versatile method for the identification of senolytic compounds","authors":"Chiara Annunziata, Francesca Castoldi, Jan Schlegel, Hazel X. Ang, Mina Ristovska, Stefania Melini, Robert Welch, Christian G. Riedel, Federico Pietrocola","doi":"10.15698/cst2023.12.292","DOIUrl":"https://doi.org/10.15698/cst2023.12.292","url":null,"abstract":"The increased burden of senescent cells is as a well-established hallmark of aging and age-related diseases. This finding sparked significant interest in the identification of molecules capable of selectively eliminating senescent cells, so-called senolytics. Here, we fine-tuned a method for the identification of senolytics that is compatible with high-content fluorescence microscopy. We used spectral detector imaging to measure the emission spectrum of unlabeled control or senescent cells. We observed that senescent cells exhibited higher levels of autofluorescence than their non-senescent counterparts, particularly in the cytoplasmic region. Building on this result, we devised a senolytic assay based on co-culturing quiescent and senescent cells, fluorescently tagged in the nuclear region through the overexpression of H2B-GFP and H2B-RFP, respectively. We validated this approach by showing that first generation senolytics were effective in reducing the number of RFP+ nuclei leaving the count of GFP+ nuclei unaffected. The result was confirmed by flow cytometry analysis of nuclei isolated from these quiescent-senescent cell co-cultures. We found that this system enables to capture cell type-specific effects of senolytics as in the case of fisetin, which kills senescent Mouse Embryonic Fibroblasts but not senescent human melanoma SK-MEL-103 cells. This approach is amenable to genetic and chemical screening for the discovery of senolytic compounds in that it overcomes the limitations of current methods, which rely upon costly chemical reagents or fluorescence microscopy using cells labeled with fluorescent cytoplasmic probes that overlap with the autofluorescence signal emitted by senescent cells.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138991430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer. sting驱动的T细胞活化:与癌症过继细胞治疗的相关性

IF 6.4

Cell Stress Pub Date : 2023-11-14 eCollection Date: 2023-11-01 DOI: 10.15698/cst2023.11.291

Fabian Richter, Christophe Paget, Lionel Apetoh

{"title":"STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer.","authors":"Fabian Richter, Christophe Paget, Lionel Apetoh","doi":"10.15698/cst2023.11.291","DOIUrl":"https://doi.org/10.15698/cst2023.11.291","url":null,"abstract":"Adoptive cell therapy (ACT) can successfully treat hematopoietic cancers but lacks efficacy against solid tumors. This is due to insufficient T cell infiltration, high tumor heterogeneity, frequent antigen loss with subsequent tumor escape, and the immunosuppressive tumor microenvironment (TME). Alternative methods to boost the anticancer efficacy of adoptively transferred cells are actively pursued. Among adjuvants that are utilized to stimulate anticancer immune responses, ligands of the stimulator of interferon genes (STING) pathway have received increasing attention. STING activation can trigger dendritic cell (DC) activation and endogenous immune responses, thereby preventing tumor escape. Activation of the STING pathway in the context of ACT was accordingly associated with improved T cell trafficking and persistence in the TME combined with the reduced presence of immunosuppressive cells. Recent findings also suggest cell-intrinsic effects of STING ligands on T cells. Activation of the STING signaling pathway was in this regard shown to enhance effector functions of CD4+ and CD8+ T cells, suggesting that the STING signaling could be exploited to harness T cell anticancer functions. In this review, we will discuss how the STING signaling can be used to enhance the anticancer efficacy of ACT.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromatin assembly factor-1 preserves genome stability in ctf4Δ cells by promoting sister chromatid cohesion. 染色质组装因子-1通过促进姐妹染色单体内聚来保持ctf4Δ细胞基因组的稳定性。

IF 6.4

Cell Stress Pub Date : 2023-09-11 DOI: 10.15698/cst2023.09.289

Nagham Ghaddar, Pierre Luciano, Vincent Géli, Yves Corda

{"title":"Chromatin assembly factor-1 preserves genome stability in ctf4Δ cells by promoting sister chromatid cohesion.","authors":"Nagham Ghaddar, Pierre Luciano, Vincent Géli, Yves Corda","doi":"10.15698/cst2023.09.289","DOIUrl":"https://doi.org/10.15698/cst2023.09.289","url":null,"abstract":"Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. Here we examined the genetic interaction between the heterotrimeric chromatin assembly factor-1 (CAF-1), a central component of chromatin assembly during replication, and the core replisome component Ctf4. We find that CAF-1 deficient cells as well as cells affected in newly-synthesized H3-H4 histones deposition during DNA replication exhibit a severe negative growth with ctf4Δ mutant. We dissected the role of CAF-1 in the maintenance of genome stability in ctf4Δ yeast cells. In the absence of CTF4, CAF-1 is essential for viability in cells experiencing replication problems, in cells lacking functional S-phase checkpoint or functional spindle checkpoint, and in cells lacking DNA repair pathways involving homologous recombination. We present evidence that CAF-1 affects cohesin association to chromatin in a DNA-damage-dependent manner and is essential to maintain cohesion in the absence of CTF4. We also show that Eco1-catalyzed Smc3 acetylation is reduced in absence of CAF-1. Furthermore, we describe genetic interactions between CAF-1 and essential genes involved in cohesin loading, cohesin stabilization, and cohesin component indicating that CAF-1 is crucial for viability when sister chromatid cohesion is affected. Finally, our data indicate that the CAF-1-dependent pathway required for cohesion is functionally distinct from the Rtt101-Mms1-Mms22 pathway which functions in replicated chromatin assembly. Collectively, our results suggest that the deposition by CAF-1 of newly-synthesized H3-H4 histones during DNA replication creates a chromatin environment that favors sister chromatid cohesion and maintains genome integrity.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10505505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response. 对癌症转移和免疫疗法反应进行灵敏、非免疫原性的体内成像。

IF 6.4

Cell Stress Pub Date : 2023-08-14 DOI: 10.15698/cst2023.08.288

Joseph R Merrill, Alessandra Inguscio, Taemoon Chung, Breanna Demestichas, Libia A Garcia, Jill Habel, David Y Lewis, Tobias Janowitz, Scott K Lyons

{"title":"Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response.","authors":"Joseph R Merrill, Alessandra Inguscio, Taemoon Chung, Breanna Demestichas, Libia A Garcia, Jill Habel, David Y Lewis, Tobias Janowitz, Scott K Lyons","doi":"10.15698/cst2023.08.288","DOIUrl":"10.15698/cst2023.08.288","url":null,"abstract":"Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [99mTc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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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