Cell Discovery最新文献_第2页

Dual-targeting strategy enables extremely potent and broad inhibition of emerging MERS-related coronaviruses. 双重靶向策略能够对新出现的中东呼吸综合征相关冠状病毒进行极其有效和广泛的抑制。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-08-26 DOI: 10.1038/s41421-025-00827-8

Fanke Jiao, Suya Jin, Qian Wang, Wei Xu, Xinling Wang, Fei Sun, Lu Lu, Shibo Jiang, Yun Zhu, Shuai Xia

引用次数: 0

A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline. 介质MED15中的磷酸化开关控制细胞衰老和认知能力下降。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-08-19 DOI: 10.1038/s41421-025-00820-1

Haozheng Li, Yuanming Zheng, Chunlei Yuan, Jiayi Wang, Xiaying Zhao, Ming Yang, Defei Xiong, Yenan Yang, Yunpeng Dai, Yiming Gao, Yuqi Wang, Lei Xue, Gang Wang

{"title":"A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline.","authors":"Haozheng Li, Yuanming Zheng, Chunlei Yuan, Jiayi Wang, Xiaying Zhao, Ming Yang, Defei Xiong, Yenan Yang, Yunpeng Dai, Yiming Gao, Yuqi Wang, Lei Xue, Gang Wang","doi":"10.1038/s41421-025-00820-1","DOIUrl":"10.1038/s41421-025-00820-1","url":null,"abstract":"A hallmark of aging is chronic systemic inflammation, which is exacerbated by the hypersecretory aging phenotype known as the senescence-associated secretory phenotype (SASP). How the SASP is initiated to accelerate tissue inflammation and aging is an outstanding question in aging biology. Here, we showed that phosphorylation of the Mediator subunit MED15 at T603 is able to control the SASP and aging. Transforming growth factor-β selectively induces CDK1-mediated MED15 T603 phosphorylation to control SASP gene expression. The MED15 T603 dephosphorylated mutant (T603A) inhibits the SASP and cell senescence, whereas the T603 phosphorylation-mimicking mutant (T603D) has the opposite effect. Mechanistically, forkhead box protein A1 preferentially binds to unphosphorylated but not phosphorylated MED15 at T603 to suppress SASP gene expression. Notably, aging mice harboring dephosphorylated mutation in this phosphosite exhibit improved learning and memory through the attenuation of the SASP across tissues. Overall, our study indicates that MED15 T603 phosphorylation serves as a control switch for SASP production, which underlies tissue aging and cognitive decline and provides a novel target for age-related pathogenesis.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"69"},"PeriodicalIF":12.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Breast cancer induces CD62L⁺ Kupffer cells via DMBT1 to promote neutrophil extracellular trap formation and liver metastasis. 乳腺癌通过DMBT1诱导CD62L+ Kupffer细胞，促进中性粒细胞胞外陷阱形成和肝脏转移。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-08-12 DOI: 10.1038/s41421-025-00819-8

Pu Tian, Qiuyao Wu, Dasa He, Wenjing Zhao, Lichao Luo, Zhenchang Jia, Wenqian Luo, Xianzhe Lv, Yanan Liu, Yuan Wang, Qian Wang, Peiyuan Zhang, Yajun Liang, Qifeng Yang, Guohong Hu

{"title":"Breast cancer induces CD62L+ Kupffer cells via DMBT1 to promote neutrophil extracellular trap formation and liver metastasis.","authors":"Pu Tian, Qiuyao Wu, Dasa He, Wenjing Zhao, Lichao Luo, Zhenchang Jia, Wenqian Luo, Xianzhe Lv, Yanan Liu, Yuan Wang, Qian Wang, Peiyuan Zhang, Yajun Liang, Qifeng Yang, Guohong Hu","doi":"10.1038/s41421-025-00819-8","DOIUrl":"10.1038/s41421-025-00819-8","url":null,"abstract":"The liver is a major target organ for breast cancer metastasis, while the regulatory mechanism of liver colonization by breast cancer remains largely unclear. Neutrophils are known to play important roles in metastatic colonization of cancer cells by the formation of neutrophil extracellular traps (NETs). Here we show the role and mechanism of a subpopulation of Kupffer cells (KCs), the liver resident macrophages, in mediating tumoral induction of NETs and liver metastasis. NETs are activated more abundantly in liver metastases of breast cancer, as compared to metastases to other organs and primary tumors. Liver-tropic tumor cells induce CD62L-expressing KCs by a secretory protein DMBT1, and CD62L+ KCs activate neutrophils for NETosis via the chemokine CCL8. Inhibition of CCL8 or its receptor on neutrophils, CCR1, impairs NETosis and metastasis. In addition, we identified a KC membrane protein MUC1 that binds to DMBT1 and subsequently activates NF-κB signaling in KCs, leading to CCL8 and CD62L expression. KCs with MUC1 inhibition effectively suppress liver metastasis. Furthermore, a DMBT1 neutralizing antibody was developed with the promise to inhibit tumor-KC interaction and treat metastatic cancer. In conclusion, our work reveals a KC subset that accounts for the liver tropism of breast cancer cells and NETs, and provides potential strategies in metastasis treatment.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"68"},"PeriodicalIF":12.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

AR to GR switch modulates differential TDO2-Kyn-AhR signalling to promote the survival and recurrence of treatment-induced dormant cells in prostate cancer. AR - GR开关调节不同的TDO2-Kyn-AhR信号传导，促进前列腺癌治疗诱导的休眠细胞的存活和复发。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-08-05 DOI: 10.1038/s41421-025-00817-w

Sangsang Li, Yifan Zhang, Maoxing Luo, Weiwei Zhou, Yitong Chen, Dinglan Wu, Qiang Wei, Yan Chang, Hailiang Hu

{"title":"AR to GR switch modulates differential TDO2-Kyn-AhR signalling to promote the survival and recurrence of treatment-induced dormant cells in prostate cancer.","authors":"Sangsang Li, Yifan Zhang, Maoxing Luo, Weiwei Zhou, Yitong Chen, Dinglan Wu, Qiang Wei, Yan Chang, Hailiang Hu","doi":"10.1038/s41421-025-00817-w","DOIUrl":"10.1038/s41421-025-00817-w","url":null,"abstract":"Cancer cells can be induced to dormancy initially by specific cancer therapies, but can be reactivated for subsequent relapse as therapy-resistant cancer cells. Although the treatment-induced dormancy-to-reactivation switch is an important process in tumour spread and recurrence, little is known about the underlying molecular mechanisms, particularly the metabolic underpinnings. In this study, we demonstrated that the tryptophan catabolism-related tryptophan 2,3-dioxygenase (TDO2) -kynurenine (Kyn) -aryl hydrocarbon receptor (AhR) signalling axis was responsible for both sustaining the survival of dormant prostate cancer cells induced by androgen deprivation therapy (ADT) and promoting the reactivation of dormant cells and their recurrent outgrowth, which facilitated the development of therapeutic resistance by allowing the dormancy-to-reactivation switch. Mechanistically, we found that ADT upregulated the expression of TDO2 to produce Kyn, which activated AhR and maintained the survival of ADT-induced dormant cells. Interestingly, the switch of transcription factors from the androgen receptor (AR) to the glucocorticoid receptor (GR) modulated the persistent expression of TDO2 and promoted the reactivation of dormant cells through the same TDO2-Kyn-AhR signalling axis. Additionally, tumour recurrence following ADT was delayed by pharmacological suppression of TDO2-Kyn-AhR signalling with a TDO2 inhibitor or an AhR inhibitor. In summary, we describe a signalling circuit mediated by tryptophan metabolism for regulating tumour cell dormancy and recurrence and propose TDO2 as a new target for the treatment of androgen-sensitive prostate cancer patients in combination with ADT.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"67"},"PeriodicalIF":12.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The second messenger c-di-AMP controls natural competence via ComFB signaling protein. 第二信使c-di-AMP通过ComFB信号蛋白控制自然能力。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-08-01 DOI: 10.1038/s41421-025-00816-x

Sherihan Samir, Sofía Doello, Andreas M Enkerlin, Erik Zimmer, Michael Haffner, Teresa Müller, Lisa Dengler, Stilianos P Lambidis, Shamphavi Sivabalasarma, Sonja-Verena Albers, Khaled A Selim

引用次数: 0

Common signatures of neutrophils in diverse disease conditions. 中性粒细胞在不同疾病条件下的共同特征。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-08-01 DOI: 10.1038/s41421-025-00818-9

Di Wu, Ying Cao, Hongjie Chen, Minghao Du, Tingting Wang, Jiarui Zhao, Mengyuan Li, Wenjing Wu, Huixuan Zhang, Ence Yang, Jing Yang, Jian Chen

引用次数: 0

Structural basis for the activity regulation of Medicago calcium channel CNGC15. 紫花苜蓿钙通道CNGC15活性调控的结构基础。

IF 12.5 1区生物学

Cell Discovery Pub Date : 2025-07-22 DOI: 10.1038/s41421-025-00815-y

Xia Xu, Qinrui Wang, Tengfei Sun, Heyi Gao, Ruichu Gu, Junzhao Yang, Jiaqi Zhou, Peng Fu, Han Wen, Guanghui Yang

引用次数: 0

Inhaled bispecific single-domain antibody BM219 for mild-to-moderate COVID-19: a double-blind, randomized, placebo-controlled phase 2 trial. 吸入双特异性单域抗体BM219治疗轻中度COVID-19：一项双盲、随机、安慰剂对照的2期试验

IF 13 1区生物学

Cell Discovery Pub Date : 2025-07-17 DOI: 10.1038/s41421-025-00813-0

Yanling Wu, Yuan Li, Ping Zhang, Siwei Guo, Fang Yuan, Vivian Liu, Ting Yu, Feng Lin, Nan Yang, Chao Tu, Hongzhou Lu, Tianlei Ying, Xin Li

引用次数: 0

The induced-fit and catalytic mechanisms of human G6PC1. 人G6PC1的诱导拟合及催化机制。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-07-15 DOI: 10.1038/s41421-025-00814-z

Qihao Chen, Yuhang Wang, Renjie Li, Qinru Bai, Yan Zhao

引用次数: 0

Decoding and reprogramming of the biosynthetic networks of mushroom-derived bioactive type II ganoderic acids in yeast. 酵母中蘑菇衍生的生物活性型灵芝酸生物合成网络的解码和重编程。

IF 13 1区生物学

Cell Discovery Pub Date : 2025-07-08 DOI: 10.1038/s41421-025-00812-1

Qin Wang, Ye Li, Shunhan Zhang, Wei Yuan, Zeqian Du, Ting Shi, Zhao Chang, Xingye Zhai, Yinhua Lu, Meng Wang, Juan Guo, Jian-Jiang Zhong, Han Xiao

{"title":"Decoding and reprogramming of the biosynthetic networks of mushroom-derived bioactive type II ganoderic acids in yeast.","authors":"Qin Wang, Ye Li, Shunhan Zhang, Wei Yuan, Zeqian Du, Ting Shi, Zhao Chang, Xingye Zhai, Yinhua Lu, Meng Wang, Juan Guo, Jian-Jiang Zhong, Han Xiao","doi":"10.1038/s41421-025-00812-1","DOIUrl":"10.1038/s41421-025-00812-1","url":null,"abstract":"Mushroom's specialized secondary metabolites possess important pharmacological activities, but their biosynthetic pathway elucidation is extremely challenging, not to mention reprogramming of their biosynthetic networks to target metabolites. By taking Ganoderma lucidum, a famous traditional medicinal mushroom, as a lead example, here we decoded the biosynthetic networks of type II ganoderic acids (TIIGAs), a group of its main bioactive metabolites by studying the coordinated gene expression in G. lucidum, identifying endogenous or heterologous enzymes capable of C22 hydroxylation, configuration conversion of C3 hydroxyl group, and acetylation on C3, C15 and C22 hydroxyl groups. Notably, we revealed the catalytic mechanism of the C22 hydroxylase CYP512W6, and an unexpected bifunctional acetyltransferase GlAT that is required to transfer acetyl groups to C15 and C22. Using a fluorescence-guided integration method, we achieved efficient biosynthesis of significant TIIGAs applicable to industrial fermentation. After introducing all the identified enzymes to baker's yeast, we observed that biosynthesis of downstream TIIGAs was severely impeded, and dredged the metabolic block by temporally regulating the expression of acetyltransferases. By reprogramming of the biosynthetic networks of TIIGAs, we were able to produce over 30 TIIGAs, exhibiting 1-4 orders of magnitude higher titers or efficiencies than those from farmed mushrooms. The work enables the access to valuable TIIGAs, facilitates their widespread application, and sheds light on research of other mushroom products.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"61"},"PeriodicalIF":13.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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