Cell Communication and Signaling最新文献

{"title":"The therapeutic potential of RNA m(6)A in lung cancer.","authors":"Jingran Yu, Wei Sun, Xiangxuan Zhao, Yingying Chen","doi":"10.1186/s12964-024-01980-5","DOIUrl":"10.1186/s12964-024-01980-5","url":null,"abstract":"<p><p>Lung cancer (LC) is a highly malignant and metastatic form of cancer. The global incidence of and mortality from LC is steadily increasing; the mean 5-year overall survival (OS) rate for LC is less than 20%. This frustrating situation may be attributed to the fact that the pathogenesis of LC remains poorly understood and there is still no cure for mid to advanced LC. Methylation at the N⁶-position of adenosine (N⁶mA) of RNA (m(6)A) is widely present in human tissues and organs, and has been found to be necessary for cell development and maintenance of homeostasis. However, numerous basic and clinical studies have demonstrated that RNA m(6)A is deregulated in many human malignancies including LC. This can drive LC malignant characteristics such as proliferation, stemness, invasion, epithelial-mesenchymal transition (EMT), metastasis, and therapeutic resistance. Intriguingly, an increasing number of studies have also shown that eliminating RNA m(6)A dysfunction can exert significant anti-cancer effects on LC such as suppression of cell proliferation and viability, induction of cell death, and reversal of treatment insensitivity. The current review comprehensively discusses the therapeutic potential of RNA m(6)A and its underlying molecular mechanisms in LC, providing useful information for the development of novel LC treatment strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"617"},"PeriodicalIF":8.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation status determines the effects of IFNγ on the expression of PD-L1 and immunomodulatory genes in melanoma.","authors":"Teitur Sævarsson, Adrián López García de Lomana, Ólafur Sánchez, Veerle van Esch, Gunnar Bjarni Ragnarsson, Siggeir Fannar Brynjólfsson, Eiríkur Steingrímsson, Berglind Ósk Einarsdóttir","doi":"10.1186/s12964-024-01963-6","DOIUrl":"https://doi.org/10.1186/s12964-024-01963-6","url":null,"abstract":"<p><strong>Background: </strong>Melanoma cells frequently dedifferentiate in response to inflammation which can increase responses to certain cytokines. Interferon-γ (IFNγ) is an integral part of the anti-tumor immune response and can directly induce both differentiational changes and expression of immunosuppressive proteins in melanoma cells. How the differentiation status of melanoma cells affects IFNγ responses remains unclear.</p><p><strong>Methods: </strong>Dedifferentiation of melanoma cells was induced via either siRNA or shRNA mediated MITF knockdown and the cells were subsequently treated with IFNγ. Effects of MITF knockdown and IFNγ treatment on gene expression were evaluated via qPCR and RNA sequencing. A Luminex assay was used to analyze the effects of dedifferentiation and IFNγ treatment on cytokine secretion. Effects on PD-L1 protein expression were analyzed via flow cytometry and western blotting. Inhibition of the JAK kinases, NF-κB and STAT3 with small molecule inhibitors, and siRNA mediated knockdown of STAT1 and IRF1 was applied to investigate the molecular mechanism behind IFNγ induced PD-L1 expression in dedifferentiated melanoma cells. The effects of inhibitor treatments and siRNA mediated knockdowns were evaluated via qPCR and western blotting. Bioinformatic analysis of publicly available RNA sequencing data, consisting of 45 patient derived melanoma cell lines, with or without IFNγ treatment, was conducted to assess the generalizability of the in vitro results.</p><p><strong>Results: </strong>Dedifferentiation renders 624Mel melanoma cells hypersensitive to IFNγ stimulation in a context-dependent manner, resulting in non-additive upregulation of IFNγ-induced genes, increased PD-L1 protein expression and amplified secretion of CCL2, CXCL10 and IL-10. Furthermore, the intensified PD-L1 protein expression occurs through the JAK-STAT1-IRF1 axis. Lastly, dedifferentiated patient derived melanoma cell lines showed enhanced inflammatory signaling in response to IFNγ compared to differentiated cells, and tended to have higher PD-L1 expression, associated with increased IRF1 expression and activity.</p><p><strong>Conclusions: </strong>Together, these findings indicate the existence of a molecular context linking dedifferentiation and IFNγ signaling in melanoma which may lead to immune evasion. Additionally, the variability in PD-L1 expression among MITF^low and MITF^high cells suggests that high IFNγ-induced PD-L1 expression associates with enhanced inflammatory gene expression. These results imply that modulating melanoma differentiation may help shape IFNγ responsiveness.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"618"},"PeriodicalIF":8.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Analysis of early effects of human APOE isoforms on Alzheimer's disease and type III hyperlipoproteinemia pathways using knock-in rat models with humanized APP and APOE.","authors":"Metin Yesiltepe, Tao Yin, Marc Tambini, Hanmei Bao, Meixia Pan, Cristina d'Abramo, Luca Giliberto, Xianlin Han, Luciano D'Adamio","doi":"10.1186/s12964-024-02004-y","DOIUrl":"https://doi.org/10.1186/s12964-024-02004-y","url":null,"abstract":"","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"619"},"PeriodicalIF":8.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal ANXA2 facilitates ovarian cancer peritoneal metastasis by activating peritoneal mesothelial cells through binding with TLR2.","authors":"Jingni Zhang, Hongmei Liu, Qiulei Wu, Tong Liu, Xiaoli Liu, Jing Cai, Xiaoqing Yi, Zehua Wang, Lingling Gao","doi":"10.1186/s12964-024-01987-y","DOIUrl":"https://doi.org/10.1186/s12964-024-01987-y","url":null,"abstract":"<p><strong>Background: </strong>Peritoneal dissemination of ovarian cancer (OvCa) can be largely attributed to the formation of a metastatic microenvironment driven by tumoral exosomes. Here, we aimed to elucidate the mechanisms through which exosomal annexin A2 (ANXA2) derived from OvCa cells induces an HPMC phenotypic shift in favour of peritoneal metastasis.</p><p><strong>Methods: </strong>Immunohistochemistry and orthotopic and intraperitoneal OvCa xenograft mouse models were used to clarify the relationship between tumour ANXA2 expression and peritoneal metastasis. Exosomes were isolated from OvCa cell lines via ultracentrifugation. Functional experiments on cell proliferation and motility, and western blot were performed to investigate the activation of HPMCs and its impact on tumour cell in vitro. High-throughput transcriptional sequencing and rescue experiments in which ANXA2 inhibitor (LCKLSL) or the toll-like receptor 2 (TLR2) inhibitor (C29) was used to co-culture the HPMCs with exosome were employed to identify the crucial functional molecules through which exosomal ANXA2 activates HPMCs. The impact of exosomal ANXA2-activated HPMCs on tumour progression was assessed via functional experiments.</p><p><strong>Results: </strong>Primary OvCa samples with high ANXA2 expression exhibited a stronger tendency to metastasize to the abdominal cavity. Tumoral ANXA2 promoted OvCa peritoneal metastasis through the secretion of exosomes carrying ANXA2. ANXA2-loaded exosomes activated HPMCs through exosomal ANXA2 binding to TLR2, shifting the phenotype of HPMCs towards mesenchymal cells, increasing their migration and invasion capacities, and elevating the expression of lipocalin 2 (LCN2). High LCN2 expression in HPMCs promoted OvCa cell adhesion, proliferation, motility, and lipid metabolism reprogramming.</p><p><strong>Conclusion: </strong>Exosomal ANXA2 secreted by tumour cells activates HPMCs and induces the expression of LCN2, which in turn promotes the peritoneal metastasis of OvCa.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"616"},"PeriodicalIF":8.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eplerenone, a mineralocorticoid receptor inhibitor, reduces cirrhosis associated changes of hepatocyte glucose and lipid metabolism.","authors":"Mohammad Mohabbulla Mohib, Sindy Rabe, Alexander Nolze, Michael Rooney, Quratul Ain, Alexander Zipprich, Michael Gekle, Barbara Schreier","doi":"10.1186/s12964-024-01991-2","DOIUrl":"https://doi.org/10.1186/s12964-024-01991-2","url":null,"abstract":"<p><strong>Background: </strong>Recent studies suggest a contribution of intrahepatic mineralocorticoid receptor (MR) activation to the development of cirrhosis. As MR blockade abrogates the development of cirrhosis and hypoxia, common during the development of cirrhosis, can activate MR in hepatocytes. But, the impact of non-physiological hepatic MR activation is unknown. In this study, we investigate the impact of hypoxia-induced hepatocyte MR activation as a relevant factor in cirrhosis.</p><p><strong>Methods: </strong>RNA sequencing followed by gene ontology term enrichment analysis was performed on liver samples from rats treated for 12 weeks with or without CCl₄ and for the last four weeks with or without eplerenone (MR antagonist). We investigated if these changes can be mimicked by hypoxia in a human hepatocyte cell line (HepG2 cells) and in primary rat hepatocytes (pRH). In order to evaluate the functional cellular importance, hepatocyte lipid accumulation, glucose consumption, lactate production and mitochondrial function were analyzed.</p><p><strong>Results: </strong>In cirrhotic liver tissue genes annotated to the GOterm \"Monocarboxylic acid metabolic process\" (PPARα, PDK4, AMACR, ABCC2, Lipin1) are downregulated. This effect is reversed by the MR antagonist eplerenone in vivo. The alterations are partially mimicked by hypoxia in rat and human hepatocytes in tissue culture. Furthermore, the reduction of mRNA and protein expression of PPARα, PDK4, AMACR, ABCC2 and Lipin1 during hypoxia is prevented by eplerenone in rat and human hepatocytes. Aldosterone, the endogenous MR agonist, did not affect the expression of those proteins in hepatocytes. As those proteins are key regulators of hepatocyte energy homeostasis, we analyzed if hypoxia affected glucose consumption, lactate production and lipid accumulation in HepG2 cells in a MR-mediated manner. All three parameters were affected by hypoxia and were partially normalized by eplerenone.</p><p><strong>Conclusion: </strong>Our findings suggest that non-physiological MR activation plays a role in the dysregulation of glucose and lipid metabolism in hepatocytes. This leads to an increase in apoptosis, probably resulting in a proinflammatory micromilieu of the hepatic tissue. The enhanced deposition of extracellular matrix contributes to the development of cirrhosis. Therefore, MR antagonists may have therapeutic potential in the treatment of early stages of liver disease due to their direct action in the liver.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"614"},"PeriodicalIF":8.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDAC10 switches NLRP3 modification from acetylation to ubiquitination and attenuates acute inflammatory diseases.","authors":"Min Yang, Zhenzhi Qin, Yueke Lin, Dapeng Ma, Caiyu Sun, Haocheng Xuan, Xiuling Cui, Wei Ma, Xinyi Zhu, Lihui Han","doi":"10.1186/s12964-024-01992-1","DOIUrl":"https://doi.org/10.1186/s12964-024-01992-1","url":null,"abstract":"<p><strong>Background: </strong>The NOD-like receptor protein (NLRP)3 inflammasome is at the signaling hub center to instigate inflammation in response to pathogen infection or oxidative stress, and its tight control is pivotal for immune defense against infection while avoiding parallel intensive inflammatory tissue injury. Acetylation of NLRP3 is critical for the full activation of NLRP3 inflammasome, while the precise regulation of the acetylation and deacetylation circuit of NLRP3 protein remained to be fully understood.</p><p><strong>Methods: </strong>The interaction between histone deacetylase 10 (HDAC10) and NLRP3 was detected by immunoprecipitation and western blot in the HDAC10 and NLRP3 overexpressing cells. The role of HDAC10 in NLRP3 inflammasome activation was measured by immunofluorescence, real-time PCR and immunoblotting assay in peritoneal macrophages and bone marrow-derived macrophages after the stimulation with LPS and ATP. To investigate the role of HDAC10 in NLRP3-involved inflammatory diseases, the Hdac10 knockout (Hdac10^-/-) mice were used to construct the LPS-induced acute endotoxemia model and folic acid-induced acute tubular necrosis model. Tissue injury level was analyzed by hematoxylin and eosin staining, and the serum level of IL-1β was measured by enzyme-linked immunosorbent assay (ELISA). The conservative analysis and immunoprecipitation assay were performed to screen the precise catalytic site regulated by HDAC10 responsible for the switching from the acetylation to ubiquitination of NLRP3.</p><p><strong>Results: </strong>Here we demonstrated that HDAC10 directly interacted with NLRP3 and induced the deacetylation of NLRP3, thus leading to the inhibition of NLRP3 inflammasome and alleviation of NLRP3 inflammasome-mediated acute inflammatory injury. Further investigation demonstrated that HDAC10 directly induced the deacetylation of NLRP3 at K496 residue, thus switching NLRP3 acetylation to the ubiquitination modification, resulting in the proteasomal degradation of NLRP3 protein. Thus, this study identified HDAC10 as a new eraser for NLRP3 acetylation, and HDAC10 attenuated NLRP3 inflammasome involved acute inflammation via directly deacetylating NLRP3.</p><p><strong>Conclusions: </strong>This study indicated that HDAC10 switched NLRP3 modification from acetylation to ubiquitination and attenuated acute inflammatory diseases, thus it provided a potential therapeutic strategy for NLRP3 inflammasome-associated diseases by targeting HDAC10.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"615"},"PeriodicalIF":8.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"V-ATPase in cancer: mechanistic insights and therapeutic potentials.","authors":"Tingting Chen, Xiaotan Lin, Shuo Lu, Bo Li","doi":"10.1186/s12964-024-01998-9","DOIUrl":"10.1186/s12964-024-01998-9","url":null,"abstract":"<p><p>Vacuolar-type H+-ATPase (V-ATPase) is a crucial proton pump that plays an essential role in maintaining intracellular pH homeostasis and a variety of physiological processes. This review provides an in-depth exploration of the structural components, functional mechanisms, and regulatory modes of V-ATPase in cancer cells. Comprising two main domains, V₁ and V₀, V-ATPase drives the proton pump through ATP hydrolysis, sustaining the pH balance within the cell and organelles. In cancer cells, the enhanced activity of V-ATPase is closely associated with the proliferation and metastasis of tumor cells, and it promotes the growth and invasion of tumor cells by regulating pH values in the tumor microenvironment. Moreover, the interaction between V-ATPase and key metabolic regulatory factors, the mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK), impacts the metabolic state of cancer cells. The role of V-ATPase in tumor drug resistance and its regulatory mechanism in non-canonical autophagy offer new perspectives and potential targets for cancer therapy. Future research directions will focus on the specific mechanisms of action of V-ATPase in the tumor microenvironment and how to translate its inhibitors into clinical applications, providing significant scientific evidence for the development of new therapeutic strategies.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"613"},"PeriodicalIF":8.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDSC: a new potential breakthrough in CAR-T therapy for solid tumors.","authors":"Nada Mohamady Farouk Abdalsalam, Abdulrahman Ibrahim, Muhammad Auwal Saliu, Tzu-Ming Liu, Xiaochun Wan, Dehong Yan","doi":"10.1186/s12964-024-01995-y","DOIUrl":"10.1186/s12964-024-01995-y","url":null,"abstract":"<p><p>Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematologic malignancies but has encountered challenges in effectively treating solid tumors. One major obstacle is the presence of the immunosuppressive tumor microenvironment (TME), which is mainly built by myeloid-derived suppressor cells (MDSCs). Recent studies have shown that MDSCs have a detrimental effect on CAR-T cells due to their potent immunosuppressive capabilities. Targeting MDSCs has shown promising results to enhance CAR-T immunotherapy in preclinical solid tumor models. In this review, we first highlight that MDSCs increase tumor proliferation, transition, angiogenesis and encourage circulating tumor cells (CTCs) extravasation leading to tumor progression and metastasis. Moreover, we describe the main characteristics of the immunosuppressive activities of MDSCs on T cells in TME. Most importantly, we summarize targeting therapeutic strategies of MDSCs in CAR-T therapies against solid tumors. These strategies include (1) therapeutic targeting of MDSCs through small molecule inhibitors and large molecule antibodies; (2) CAR-T targeting cancer cell antigen combination with MDSC modulatory agents; (3) cytokine receptor antigen-targeted CAR-T indirectly or directly targeting MDSCs reshapes TME; (4) modified natural killer (NK) cells expressing activating receptor directly targeting MDSCs; and (5) CAR-T directly targeting MDSC selective antigens. In the near future, we are expected to witness the improvement of CAR-T cell therapies for solid tumors by targeting MDSCs in clinical practice.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"612"},"PeriodicalIF":8.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4.","authors":"Guanwen Wang, Ping Wen, Ting Xue, Yuxin Huang, Qing Shao, Ningning Zhang, Fanli Qu, Jing Wang, Nan Wang, Xiaohua Zeng","doi":"10.1186/s12964-024-02000-2","DOIUrl":"https://doi.org/10.1186/s12964-024-02000-2","url":null,"abstract":"<p><p>Early dissemination refers to the process by which cancer cells spread to distant organs at an early stage of the disease, often before the primary tumor is clinically detectable. Experimental studies have demonstrated that Her2 promotes early dissemination of breast cancer by inhibiting the p38 signaling pathway. However, the precise mechanism by which Her2 suppresses the activation of p38 signaling in early-stage cancer cells (ECCs) remains unclear. Here, we report that MAP3K4, an upstream kinase of p38, is downregulated in Her2 + ductal carcinoma in situ (DCIS) cells and tissues, which is required for Her2-induced early dissemination of DCIS cells by regulating the activation of the p38 signaling cascade. Furthermore, Her2 suppresses the transcription of MAP3K4 by downregulating the expression of HOXB13, a crucial transcription factor contributing to MAP3K4 expression in DCIS cells. Together, these findings unveil a novel downstream regulatory mechanism through which Her2 inhibits the activation of p38 signaling and facilitates early dissemination of breast cancer, offering insights into the development of effective diagnostic methods and targeted therapies for inhibiting the early dissemination of Her2 + breast cancer.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"611"},"PeriodicalIF":8.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PGC7 regulates maternal mRNA translation via AKT1-YBX1 interactions in mouse oocytes.","authors":"Yingxiang Liu, Peiwen Feng, Xing Wei, Hongyu Xu, Mengying Yu, Lei Zhang, Weijie Hao, Zekun Guo","doi":"10.1186/s12964-024-01976-1","DOIUrl":"https://doi.org/10.1186/s12964-024-01976-1","url":null,"abstract":"<p><p>Timely and accurate translation of maternal mRNA is essential for oocyte maturation and early embryonic development. Previous studies have highlighted the importance of Primordial Germ cell 7 (PGC7) as a maternal factor in maintaining DNA methylation of maternally imprinted loci in zygotes. However, it is still unknown whether PGC7 is involved in the regulation of Maternal mRNA Translation. In this study, we have identified that PGC7-AKT1-YBX1 axis is involved in promoting the translation of maternal mRNAs. PGC7 not only sustains AKT1 activity by counteracting PP2A dephosphorylation and facilitating PDK1-AKT1 binding but also assists AKT1 in phosphorylating the translation inhibitor YBX1. In the absence of PGC7, despite increased PIK3CA expression and AKT1 phosphorylation, AKT1 is unable to phosphorylate YBX1. PGC7 facilitates the interaction between AKT1 and YBX1, enhancing YBX1-Serine 100 phosphorylation, which leads to YBX1 dissociation from eIF4E, thereby activating the translation of maternal Cyclin B1 and YAP1. The findings demonstrate the indispensability of PGC7 for translation activation in mammalian oocytes and provide a potential network regulated by PGC7 in early oogenesis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"22 1","pages":"604"},"PeriodicalIF":8.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}