Cell Communication and Signaling最新文献

{"title":"Mitochondrion-based organellar therapies for central nervous system diseases.","authors":"Mengke Zhao, Jiayi Wang, Shuaiyu Zhu, Meina Wang, Chong Chen, Liang Wang, Jing Liu","doi":"10.1186/s12964-024-01843-z","DOIUrl":"10.1186/s12964-024-01843-z","url":null,"abstract":"<p><p>As most traditional drugs used to treat central nervous system (CNS) diseases have a single therapeutic target, many of them cannot treat complex diseases or diseases whose mechanism is unknown and cannot effectively reverse the root changes underlying CNS diseases. This raises the question of whether multiple functional components are involved in the complex pathological processes of CNS diseases. Organelles are the core functional units of cells, and the replacement of damaged organelles with healthy organelles allows the multitargeted and integrated modulation of cellular functions. The development of therapies that target independent functional units in the cell, specifically, organelle-based therapies, is rapidly progressing. This article comprehensively discusses the pathogenesis of mitochondrial homeostasis disorders, which involve mitochondria, one of the most important organelles in CNS diseases, and the machanisms of mitochondrion-based therapies, as well as current preclinical and clinical studies on the efficacy of therapies targeting mitochondrial to treat CNS diseases, to provide evidence for use of organelle-based treatment strategies in the future.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402071","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}

{"title":"TMEM132A regulates Wnt/β-catenin signaling through stabilizing LRP6 during mouse embryonic development.","authors":"Shin Ae Oh, Jiyeon Jeon, Su-Yeon Je, Seoyoung Kim, Joohyun Jung, Hyuk Wan Ko","doi":"10.1186/s12964-024-01855-9","DOIUrl":"10.1186/s12964-024-01855-9","url":null,"abstract":"<p><p>The Wnt/β-catenin signaling pathway is crucial for embryonic development and adult tissue homeostasis. Dysregulation of Wnt signaling is linked to various developmental anomalies and diseases, notably cancer. Although numerous regulators of the Wnt signaling pathway have been identified, their precise function during mouse embryo development remains unclear. Here, we revealed that TMEM132A is a crucial regulator of canonical Wnt/β-catenin signaling in mouse development. Mouse embryos lacking Tmem132a displayed a range of malformations, including open spina bifida, caudal truncation, syndactyly, and renal defects, similar to the phenotypes of Wnt/β-catenin mutants. Tmem132a knockdown in cultured cells suppressed canonical Wnt/β-catenin signaling. In developing mice, loss of Tmem132a also led to diminished Wnt/β-catenin signaling. Mechanistically, we showed that TMEM132A interacts with the Wnt co-receptor LRP6, thereby stabilizing it and preventing its lysosomal degradation. These findings shed light on a novel role for TMEM132A in regulating LRP6 stability and canonical Wnt/β-catenin signaling during mouse embryo development. This study provides valuable insights into the molecular intricacies of the Wnt signaling pathway. Further research may deepen our understanding of Wnt pathway regulation and offer its potential therapeutic applications.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395481","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}

{"title":"Elucidating the power of arginine restriction: taming type I interferon response in breast cancer via selective autophagy.","authors":"Apsana Lamsal, Sonja Benedikte Andersen, Ida Johansson, Marie-Catherine Drigeard Desgarnier, Camilla Wolowczyk, Nikolai Engedal, Marina Vietri, Geir Bjørkøy, Miriam S Giambelluca, Kristine Pettersen","doi":"10.1186/s12964-024-01858-6","DOIUrl":"10.1186/s12964-024-01858-6","url":null,"abstract":"<p><strong>Background: </strong>Type I interferons (IFN-I) are potent alarm factors that initiate cancer cell elimination within tumors by the immune system. This critical immune response is often suppressed in aggressive tumors, thereby facilitating cancer immune escape and unfavorable patient outcome. The mechanisms underpinning IFN-I suppression in tumors are incompletely understood. Arginase-1 (ARG1)-expressing immune cells that infiltrate tumors can restrict arginine availability by ARG1-mediated arginine degradation. We hypothesized that arginine restriction suppresses the IFN-I response in tumors.</p><p><strong>Methods: </strong>Comprehensive, unbiased open approach omics analyses, various in vitro techniques, including microscopy, qPCR, immunoblotting, knock-down experiments, and flow cytometry were employed, as well as ex vivo analysis of tumor tissue from mice. Several functional bioassays were utilized to assess metabolic functions and autophagy activity in cancer cells.</p><p><strong>Results: </strong>Arginine restriction potently induced expression of selective autophagy receptors, enhanced bulk and selective autophagy and strongly suppressed the IFN-I response in cancer cells in an autophagy-dependent manner.</p><p><strong>Conclusion: </strong>Our study proposes a mechanism for how tumor-infiltrating immune cells can promote cancer immune escape by dampening the IFN-I response. We suggest ARG1 and autophagy as putative therapeutic targets to activate the IFN-I response in tumors.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395478","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}

{"title":"Correction: SUMOylation-induced membrane localization of TRPV1 suppresses proliferation and migration in gastric cancer cells.","authors":"Yang Yang, Xiaokun Gu, Weiji Weng, Jinke Cheng, Ou Huang, Si-Jian Pan, Yong Li","doi":"10.1186/s12964-024-01864-8","DOIUrl":"https://doi.org/10.1186/s12964-024-01864-8","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395477","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}

{"title":"Senescent cells promote breast cancer cells motility by secreting GM-CSF and bFGF that activate the JNK signaling pathway.","authors":"Nan Wang, Yan Fang, Yigong Hou, Dongmei Cheng, Emily V Dressler, Hao Wang, Juan Wang, Guanwen Wang, Yilei Li, Hong Liu, Rong Xiang, Shuang Yang, Peiqing Sun","doi":"10.1186/s12964-024-01861-x","DOIUrl":"https://doi.org/10.1186/s12964-024-01861-x","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis.</p><p><strong>Methods: </strong>In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility.</p><p><strong>Results: </strong>Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models.</p><p><strong>Conclusions: </strong>These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395480","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}

{"title":"Correction: Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.","authors":"Jieon Hwang, Areum Park, Chinwoo Kim, Chang Gon Kim, Jaesung Kwak, Byungil Kim, Hyunjin Shin, Minhee Ku, Jaemoon Yang, Ayoung Baek, Jiwon Choi, Hocheol Lim, Kyoung Tai No, Xianghua Zhao, Uyeong Choi, Tae Il Kim, Kyu-Sung Jeong, Hyuk Lee, Sang Joon Shin","doi":"10.1186/s12964-024-01840-2","DOIUrl":"https://doi.org/10.1186/s12964-024-01840-2","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395476","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}

{"title":"Role of scaffold proteins in the heterogeneity of glioblastoma.","authors":"Varun J Iyer, John E Donahue, Mahasin A Osman","doi":"10.1186/s12964-024-01809-1","DOIUrl":"10.1186/s12964-024-01809-1","url":null,"abstract":"<p><p>Glioblastoma (GB) is a highly heterogeneous type of incurable brain cancer with a low survival rate. Intensive ongoing research has identified several potential targets; however, GB is marred by the activation of multiple pathways, and thus common targets are highly sought. The signal regulatory scaffold IQGAP1 is an oncoprotein implicated in GB. IQGAP1 nucleates a myriad of pathways in a contextual manner and modulates many of the targets altered in GB like MAPK, NF-κB, and mTOR/PI3K/Akt1, thus positioning it as a plausible common therapeutic target. Here, we review the targets that are subjects of GB treatment clinical trials and the commonly used animal models that facilitate target identification. We propose a model in which the dysfunction of various IQGAP1 pathways can explain to a larger extent some of the GB heterogeneity and offer a platform for personalized medicine.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395479","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}

{"title":"GZMA suppressed GPX4-mediated ferroptosis to improve intestinal mucosal barrier function in inflammatory bowel disease.","authors":"Rongwei Niu, Jiaoli Lan, Danxia Liang, Li Xiang, Jiaxin Wu, Xiaoyan Zhang, Zhiling Li, Huan Chen, Lanlan Geng, Wanfu Xu, Sitang Gong, Min Yang","doi":"10.1186/s12964-024-01836-y","DOIUrl":"10.1186/s12964-024-01836-y","url":null,"abstract":"<p><strong>Background: </strong>Our previous study has demonstrated a decreased colonic CD8⁺CD39⁺ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown.</p><p><strong>Methods: </strong>Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function.</p><p><strong>Results: </strong>Herein, we, for the first time, demonstrated that CD8⁺CD39⁺ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo.</p><p><strong>Conclusion: </strong>These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376348","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}

{"title":"Peroxisomal homeostasis in metabolic diseases and its implication in ferroptosis.","authors":"Jiwei Han, Daheng Zheng, Pu-Ste Liu, Shanshan Wang, Xin Xie","doi":"10.1186/s12964-024-01862-w","DOIUrl":"10.1186/s12964-024-01862-w","url":null,"abstract":"<p><p>Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376349","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}

{"title":"STAT3 blockade ameliorates LPS-induced kidney injury through macrophage-driven inflammation.","authors":"Song-Hee Lee, Kyu Hong Kim, Seong Min Lee, Seong Joon Park, Sunhwa Lee, Ran-Hui Cha, Jae Wook Lee, Dong Ki Kim, Yon Su Kim, Sang-Kyu Ye, Seung Hee Yang","doi":"10.1186/s12964-024-01841-1","DOIUrl":"10.1186/s12964-024-01841-1","url":null,"abstract":"<p><strong>Background: </strong>Signal transducer and activator of transcription 3 (STAT3), a multifaceted transcription factor, modulates host immune responses by activating cellular response to signaling ligands. STAT3 has a pivotal role in the pathophysiology of kidney injury by counterbalancing resident macrophage phenotypes under inflammation conditions. However, STAT3's role in acute kidney injury (AKI), particularly in macrophage migration, and in chronic kidney disease (CKD) through fibrosis development, remains unclear.</p><p><strong>Methods: </strong>Stattic (a JAK2/STAT3 inhibitor, 5 mg/kg or 10 mg/kg) was administered to evaluate the therapeutic effect on LPS-induced AKI (L-AKI) and LPS-induced CKD (L-CKD), with animals sacrificed 6-24 h and 14 days post-LPS induction, respectively. The immune mechanisms of STAT3 blockade were determined by comparing the macrophage phenotypes and correlated with renal function parameters. Also, the transcriptomic analysis was used to confirm the anti-inflammatory effect of L-AKI, and the anti-fibrotic role was further evaluated in the L-CKD model.</p><p><strong>Results: </strong>In the L-AKI model, sequential increases in BUN and blood creatinine levels were time-dependent, with a marked elevation of 0-6 h after LPS injection. Notably, two newly identified macrophage subpopulations (CD11b^highF4/80^low and CD11b^lowF4/80^high), exhibited population changes, with an increase in the CD11b^highF4/80^low population and a decrease in the CD11b^lowF4/80^high macrophages. Corresponding to the FACS results, the tubular injury score, NGAL, F4/80, and p-STAT3 expression in the tubular regions were elevated. STAT3 inhibitor injection in L-AKI and L-CKD mice reduced renal injury and fibrosis. M2-type subpopulation with CD206 in CD11b^lowF4/80^high population increased in the Stattic-treated group compared with that in the LPS-alone group in the L-AKI model. Additionally, STAT3 inhibitor reduced inflammation driven by LPS-stimulated macrophages and epithelial cells injury in the co-culture system. Transcriptomic profiling identified 3 common genes in the JAK-STAT, TLR, and TNF signaling pathways and 11 common genes in the LPS with macrophage response. The PI3K-AKT (IL-6, Akt3, and Pik3r1) and JAK-STAT pathways were determined as potential Stattic targets. Further confirmation through mRNA and protein expressions analyses showed that Stattic treatment reduced inflammation in the L-AKI and fibrosis in the L-CKD mice.</p><p><strong>Conclusions: </strong>STAT3 blockade effectively mitigated inflammation by retrieving the CD11b^lowF4/80^high population, further emphasizing the role of STAT3-associated macrophage-driven inflammation in kidney injury.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11453053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376350","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}