Cell Stress最新文献_第7页

A sympathetic gut connection drives the metabolic benefits of Roux-en-Y gastric bypass. 交感肠连接驱动Roux-en-Y胃旁路术的代谢益处。

IF 6.4

Cell Stress Pub Date : 2020-11-24 DOI: 10.15698/cst2020.12.236

Mohammed K Hankir

引用次数: 2

TLR4: the fall guy in sepsis? TLR4:败血症的替罪羊?

IF 6.4

Cell Stress Pub Date : 2020-11-09 DOI: 10.15698/cst2020.12.237

Joseph Menassa, Christina Nedeva, Corey Pollock, Hamsa Puthalakath

{"title":"TLR4: the fall guy in sepsis?","authors":"Joseph Menassa, Christina Nedeva, Corey Pollock, Hamsa Puthalakath","doi":"10.15698/cst2020.12.237","DOIUrl":"https://doi.org/10.15698/cst2020.12.237","url":null,"abstract":"Sepsis and its impact on human health can be traced back to 1000 BC and continues to be a major health burden today. It causes about 11 million deaths world-wide of which, more than a third are due to neonatal sepsis. There is no effective treatment other than fluid resuscitation therapy and antibiotic treatment that leave patients immunosuppressed and vulnerable to nosocomial infections. Added to that, ageing population and the emergence of antibiotic resistant bacteria pose new challenges. Most of the deleterious effects of sepsis are due to the host response to the systemic infection. In the initial phase of infection, hyper activation of the immune system leads to cytokine storm, which could lead to organ failure and this accounts for about 15% of overall deaths. However, the subsequent immune paralysis phase (mostly attributed to apoptotic death of immune cells) accounts for about 85% of all deaths. Past clinical trials (more than 100 in the last 30 years) all targeted the inflammatory phase with little success, predictably, for inflammation is a necessary process to fight infection. In order to identify the regulators of immune cell death during sepsis, we carried out an unbiased, whole genome CRISPR screening in mice and identified Trigger Receptor Expressed in Myeloid-like 4 (Treml4) as the receptor that controls both the inflammatory phase and the immune suppression phase in sepsis (Nedeva et al. (2020) Nature Immunol, doi: 10.1038/s41590-020-0789-z). Characterising the Treml4 gene knockout mice revealed new insights into the relative roles of TLR4 and TREML4 in inducing the inflammatory cytokine storm during sepsis.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 12","pages":"270-272"},"PeriodicalIF":6.4,"publicationDate":"2020-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38736466","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: 4

A mutant p53/Hif1α/miR-30d axis reprograms the secretory pathway promoting the release of a prometastatic secretome. 突变的p53/Hif1α/miR-30d轴重编程分泌途径，促进原转移性分泌组的释放。

IF 6.4

Cell Stress Pub Date : 2020-10-05 DOI: 10.15698/cst2020.11.235

Valeria Capaci, Fiamma Mantovani, Giannino Del Sal

{"title":"A mutant p53/Hif1α/miR-30d axis reprograms the secretory pathway promoting the release of a prometastatic secretome.","authors":"Valeria Capaci, Fiamma Mantovani, Giannino Del Sal","doi":"10.15698/cst2020.11.235","DOIUrl":"https://doi.org/10.15698/cst2020.11.235","url":null,"abstract":"TP53 missense mutations are frequent driver events during tumorigenesis. The majority of TP53 mutations are missense and occur within the DNA binding domain of p53, leading to expression of mutant p53 (mut-p53) proteins that not only lose the tumor suppressive functions of the wild-type (wt-p53) form, but can also acquire novel oncogenic features fostering tumor growth, metastasis and chemoresistance. Mut-p53 affects fundamental cellular pathways and functions through different mechanisms, a major one being the alteration of gene expression. In our recent work (Capaci et al., 2020, Nat Commun) we found that mut-p53, via miR-30d, modifies structure and function of the Golgi apparatus (GA) and induces increased rate of trafficking. This culminates in the release of a pro-malignant secretome, which is capable of remodeling the tumor microenvironment (TME), to increase stiffness of the extracellular matrix (ECM), favouring metastatic colonization, as shown by cell-based assays and experiments of metastatic niche preconditioning in mouse xenograft models. This study provides new insights into the mechanisms by which mut-p53, through induction of non-coding RNAs, can exert pro-tumorigenic functions in a non-cell-autonomous fashion, and highlights potential non-invasive biomarkers and therapeutic targets to treat tumors harboring mut-p53 (Figure 1).","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 11","pages":"261-264"},"PeriodicalIF":6.4,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38569855","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: 1

Targeting the TGFβ pathway in uterine carcinosarcoma. 靶向子宫癌肉瘤中TGFβ通路。

IF 6.4

Cell Stress Pub Date : 2020-08-25 DOI: 10.15698/cst2020.11.234

Shailendra Kumar Dhar Dwivedi, Geeta Rao, Anindya Dey, Megan Buechel, Yushan Zhang, Min Zhang, Da Yang, Priyabrata Mukherjee, Resham Bhattacharya

{"title":"Targeting the TGFβ pathway in uterine carcinosarcoma.","authors":"Shailendra Kumar Dhar Dwivedi, Geeta Rao, Anindya Dey, Megan Buechel, Yushan Zhang, Min Zhang, Da Yang, Priyabrata Mukherjee, Resham Bhattacharya","doi":"10.15698/cst2020.11.234","DOIUrl":"10.15698/cst2020.11.234","url":null,"abstract":"Uterine carcinosarcoma (UCS) is a relatively infrequent, but extremely aggressive endometrial malignancy. Although surgery and chemotherapy have improved outcomes, overall survival (OS) remains dismal due to the lack of targeted therapy and biphasic (epithelial and mesenchymal) nature that renders the tumor aggressive and difficult to manage. Here we report a role of transforming growth factor-β (TGFβ) in maintaining epithelial to mesenchymal transition (EMT) phenotype and aggressiveness in UCS. Using a 3D-culture system, we evaluated the efficacy of the transforming growth factor-β receptor-I (TGFβR1) kinase inhibitor Galunisertib (GLT), alone and in combination with standard chemotherapeutic drugs used for the management of UCS. We demonstrate that GLT by inhibiting canonical and non-canonical signaling emanating from transforming growth factor-β1 (TGFβ1) reduces cellular viability, invasion, clonal growth and differentiation. Interestingly, GLT sensitizes UCS cells to chemotherapy both in vitro and in in vivo preclinical tumor model. Hence, targeting TGFβ signaling, in combination with standard chemotherapy, may be exploited as an important strategy to manage the clinically challenging UCS.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 11","pages":"252-260"},"PeriodicalIF":6.4,"publicationDate":"2020-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38569856","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: 8

Endocytosis in the adaptation to cellular stress. 胞吞作用在适应细胞应激中的作用。

IF 6.4

Cell Stress Pub Date : 2020-08-18 DOI: 10.15698/cst2020.10.232

Tania López-Hernández, Volker Haucke, Tanja Maritzen

{"title":"Endocytosis in the adaptation to cellular stress.","authors":"Tania López-Hernández, Volker Haucke, Tanja Maritzen","doi":"10.15698/cst2020.10.232","DOIUrl":"10.15698/cst2020.10.232","url":null,"abstract":"Cellular life is challenged by a multitude of stress conditions, triggered for example by alterations in osmolarity, oxygen or nutrient supply. Hence, cells have developed sophisticated stress responses to cope with these challenges. Some of these stress programs such as the heat shock response are understood in great detail, while other aspects remain largely elusive including potential stress-dependent adaptations of the plasma membrane proteome. The plasma membrane is not only the first point of encounter for many types of environmental stress, but given the diversity of receptor proteins and their associated molecules also represents the site at which many cellular signal cascades originate. Since these signaling pathways affect virtually all aspects of cellular life, changes in the plasma membrane proteome appear ideally suited to contribute to the cellular adaptation to stress. The most rapid means to alter the cell surface proteome in response to stress is by alterations in endocytosis. Changes in the overall endocytic flux or in the endocytic regulation of select proteins conceivably can help to counteract adverse environmental conditions. In this review we summarize recent data regarding stress-induced changes in endocytosis and discuss how these changes might contribute to the cellular adaptation to stress in different systems. Future studies will be needed to uncover the underlying mechanisms in detail and to arrive at a coherent picture.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 10","pages":"230-247"},"PeriodicalIF":6.4,"publicationDate":"2020-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38462553","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: 27

Exocytotic fusion pore under stress. 压力下的外吞融合孔。

IF 4.1

Cell Stress Pub Date : 2020-08-10 DOI: 10.15698/cst2020.09.230

Helena Haque Chowdhury, Robert Zorec

{"title":"Exocytotic fusion pore under stress.","authors":"Helena Haque Chowdhury, Robert Zorec","doi":"10.15698/cst2020.09.230","DOIUrl":"10.15698/cst2020.09.230","url":null,"abstract":"Exocytosis is a universal process of eukaryotic cells, consisting of fusion between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a channel through which vesicle cargo exits into the extracellular space. In 1986, Rand and Parsegian proposed several stages to explain the nature of membrane fusion. Following stimulation, it starts with focused stress destabilization of membranes in contact, followed by the coalescence of two membrane surfaces. In the next fraction of a millisecond, restabilization of fused membranes is considered to occur to maintain the cell's integrity. This view predicted that once a fusion pore is formed, it must widen abruptly, irreversibly and fully, whereby the vesicle membrane completely integrates with and collapses into the plasma membrane (full fusion exocytosis). However, recent experimental evidence has revealed that once the fusion pore opens, it may also reversibly close (transient or kiss-and-run exocytosis). Here, we present a historical perspective on understanding the mechanisms that initiate the membrane merger and fusion pore formation. Next, post-fusion mechanisms that regulate fusion pore stability are considered, reflecting the state in which the forces of widening and constriction of fusion pores are balanced. Although the mechanisms generating these forces are unclear, they may involve lipids and proteins, including SNAREs, which play a role not only in the pre-fusion but also post-fusion stages of exocytosis. How molecules stabilize the fusion pore in the open state is key for a better understanding of fusion pore physiology in health and disease.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 9","pages":"218-226"},"PeriodicalIF":4.1,"publicationDate":"2020-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38362456","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

Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy. 靶向免疫检查点抑制剂MEK抑制剂与激动剂抗cd40抗体联合治疗的耐药机制。

IF 6.4

Cell Stress Pub Date : 2020-08-06 DOI: 10.15698/cst2020.10.233

Daniel Baumann, Rienk Offringa

{"title":"Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy.","authors":"Daniel Baumann, Rienk Offringa","doi":"10.15698/cst2020.10.233","DOIUrl":"https://doi.org/10.15698/cst2020.10.233","url":null,"abstract":"The widespread application of immune-checkpoint blockade (ICB) has resulted in unprecedented response rates in patients with immunogenic cancers, such as melanoma and lung cancer. However, sub-groups of patients with these indications do not respond to ICB, and the same applies to patients with other cancer types. Mechanisms of resistance to ICB include low tumor immunogenicity associated with low T cell infiltration ('cold' tumors), suppression of anti-tumor immunity by immunosuppressive cells in the tumor microenvironment (TME), lack of antigen-presentation and immune escape (e.g. by downregulation of MHC-I on tumor cells) as well as oncologic pathways that suppress immune responses. Combination strategies, involving cytostatic drugs, harbor the potential to overcome refractoriness to immunotherapy. However, suppression of immune cell function by cytostatic drugs may limit the efficacy. In our study, we show that combination treatment of targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) and agonist immunostimulatory anti-CD40 antibody (Ab) is particularly suitable in counteracting aforementioned ICB resistance mechanisms (Fig. 1).","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 10","pages":"248-251"},"PeriodicalIF":6.4,"publicationDate":"2020-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38462552","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: 3

Hyaluronan goes to great length. 透明质酸的作用很长。

IF 6.4

Cell Stress Pub Date : 2020-07-17 DOI: 10.15698/cst2020.09.231

Vera Gorbunova, Masaki Takasugi, Andrei Seluanov

{"title":"Hyaluronan goes to great length.","authors":"Vera Gorbunova, Masaki Takasugi, Andrei Seluanov","doi":"10.15698/cst2020.09.231","DOIUrl":"https://doi.org/10.15698/cst2020.09.231","url":null,"abstract":"Hyaluronan is a major non-protein component of extracellular matrix that affects biomechanical properties of tissues and interacts with cell receptors. Hyaluronan is a linear glycosaminoglycan composed of repeating disaccharides of (β, 1-4)-glucuronic acid (GlcUA) and (β, 1-3)-N-acetyl glucosamine (GlcNAc). The length of hyaluronan can range from an oligomer to an extremely long form up to millions of daltons. The concept that emerged in the field is that high (HMW-HA) and low (LMW-HA) molecular weight hyaluronans have different biological properties and trigger different signaling cascades within the cells. LMW-HA is associated with inflammation, tissue injury and metastasis, while HMW-HA improves tissue homeostasis and has anti-inflammatory and antimetastatic properties. HMW-HA is used in the clinic to treat arthritis, and as a filler in surgery and in the form of rinses to treat local inflammation. However, HMW-HA products used in the clinic come in a range of sizes between 0.5-6 mDa that are used interchangeably. Remarkably, the tissues of a long-lived and cancer-resistant rodent, the naked mole rat, contain abundant HA of very high molecular weight. While human fibroblasts secrete HA up to 2 MDa, naked mole rat fibroblasts produce HA of 6-12 MDa. Does this very high HMW-HA (vHMW-HA) differ functionally from HMW-HA? We found that vHMW-HA has superior cytoprotective properties compared to HMW-HA, and interacts differently with the CD44 receptor leading to distinct transcriptional changes (Takasugi et al. (2020), Nat Commun). These results indicate that vHMW-HA has greater therapeutic benefits than the standard HMW-HA.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 9","pages":"227-229"},"PeriodicalIF":6.4,"publicationDate":"2020-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38459336","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: 6

PRMT5 function and targeting in cancer. PRMT5在癌症中的功能和靶向性。

IF 6.4

Cell Stress Pub Date : 2020-07-13 DOI: 10.15698/cst2020.08.228

Hyungsoo Kim, Ze'ev A Ronai

引用次数: 85

Regulation of immune checkpoint blockade efficacy in breast cancer by FIP200: A canonical-autophagy-independent function. FIP200对乳腺癌免疫检查点阻断疗效的调节:一种典型的自噬独立功能。

IF 6.4

Cell Stress Pub Date : 2020-07-02 DOI: 10.15698/cst2020.08.229

Syn Kok Yeo, Jun-Lin Guan

{"title":"Regulation of immune checkpoint blockade efficacy in breast cancer by FIP200: A canonical-autophagy-independent function.","authors":"Syn Kok Yeo, Jun-Lin Guan","doi":"10.15698/cst2020.08.229","DOIUrl":"https://doi.org/10.15698/cst2020.08.229","url":null,"abstract":"Immune checkpoint blockade (ICB) has emerged as a promising therapeutic strategy because of its potential to induce durable therapeutic responses in cancer patients. However, in the case of breast cancer, its application and efficacy has been limited. As such, combinatorial therapeutic strategies that can unlock the potential of ICB in breast cancer are of urgent need. In view of that, autophagy-related proteins that play a role in the autophagic cell recycling process have been implicated in the regulation of inflammatory and anti-tumor immune responses. Accordingly, autophagy-related proteins represent a group of prospective therapeutic targets in conjunction with ICB. In our recent study (Okamoto T et al. (2020), Cancer Res), we developed immune-competent mouse models of breast cancer which were deficient for the autophagic function of FIP200 or had FIP200 completely ablated to test the efficacy of ICB. We showed that although FIP200's autophagy function was required for progression of PyMT-driven mammary tumors, FIP200's canonical-autophagy-independent function was responsible for increased T-cell infiltration, IFN-signaling and ICB efficacy. These findings provide genetic proof of principle for a combinatorial therapeutic strategy that involves ablation of FIP200 to improve ICB efficacy in non-responsive breast cancers.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 8","pages":"216-217"},"PeriodicalIF":6.4,"publicationDate":"2020-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38228743","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: 1