Cell Research最新文献_第10页

Nociceptor neurons promote PDAC progression and cancer pain by interaction with cancer-associated fibroblasts and suppression of natural killer cells 痛觉感受器神经元通过与癌症相关成纤维细胞和抑制自然杀伤细胞的相互作用促进PDAC的进展和癌症疼痛

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-24 DOI: 10.1038/s41422-025-01098-4

Kaiyuan Wang, Bo Ni, Yongjie Xie, Zekun Li, Limei Yuan, Chenyang Meng, Tiansuo Zhao, Song Gao, Chongbiao Huang, Hongwei Wang, Ying Ma, Tianxing Zhou, Yukuan Feng, Antao Chang, Chao Yang, Jun Yu, Wenwen Yu, Fenglin Zang, Yanhui Zhang, Ru-Rong Ji, Xiuchao Wang, Jihui Hao

{"title":"Nociceptor neurons promote PDAC progression and cancer pain by interaction with cancer-associated fibroblasts and suppression of natural killer cells","authors":"Kaiyuan Wang, Bo Ni, Yongjie Xie, Zekun Li, Limei Yuan, Chenyang Meng, Tiansuo Zhao, Song Gao, Chongbiao Huang, Hongwei Wang, Ying Ma, Tianxing Zhou, Yukuan Feng, Antao Chang, Chao Yang, Jun Yu, Wenwen Yu, Fenglin Zang, Yanhui Zhang, Ru-Rong Ji, Xiuchao Wang, Jihui Hao","doi":"10.1038/s41422-025-01098-4","DOIUrl":"10.1038/s41422-025-01098-4","url":null,"abstract":"The emerging field of cancer neuroscience has demonstrated great progress in revealing the crucial role of the nervous system in cancer initiation and progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized by perineural invasion and modulated by autonomic (sympathetic and parasympathetic) and sensory innervations. Here, we further demonstrated that within the tumor microenvironment of PDAC, nociceptor neurons interacted with cancer-associated fibroblasts (CAFs) through calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF). This interaction led to the inhibition of interleukin-15 expression in CAFs, suppressing the infiltration and cytotoxic function of natural killer (NK) cells and thereby promoting PDAC progression and cancer pain. In PDAC patients, nociceptive innervation of tumor tissue is negatively correlated with the infiltration of NK cells while positively correlated with pain intensity. This association serves as an independent prognostic factor for both overall survival and relapse-free survival for PDAC patients. Our findings highlight the crucial regulation of NK cells by nociceptor neurons through interaction with CAFs in the development of PDAC. We also propose that targeting nociceptor neurons or CGRP signaling may offer a promising therapy for PDAC and cancer pain.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 5","pages":"362-380"},"PeriodicalIF":25.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Target DNA-induced filament formation and nuclease activation of SPARDA complex 靶dna诱导丝的形成和SPARDA复合体的核酸酶激活

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-24 DOI: 10.1038/s41422-025-01100-z

Feng Wang, Haijiang Xu, Chendi Zhang, Jialin Xue, Zhuang Li

{"title":"Target DNA-induced filament formation and nuclease activation of SPARDA complex","authors":"Feng Wang, Haijiang Xu, Chendi Zhang, Jialin Xue, Zhuang Li","doi":"10.1038/s41422-025-01100-z","DOIUrl":"10.1038/s41422-025-01100-z","url":null,"abstract":"The short Argonaute-based bacterial defense system, SPARDA (Short Prokaryotic Argonaute and DNase/RNase-APAZ), utilizes guide RNA to target invading complementary DNA and exhibits collateral nuclease activity, leading to cell death or dormancy. However, its detailed mechanisms remain poorly understood. In this study, we investigated the SPARDA system from Novosphingopyxis baekryungensis (NbaSPARDA) and discovered an unexpected filament configuration upon target DNA binding, which strongly correlated with collateral nuclease activity. Filament formation and nuclease activation require a guide–target heteroduplex of sufficient length with perfect complementarity at the central region. A series of cryo-EM structures of NbaSPARDA complexes, loaded with guide RNA, target DNA of varying lengths, and substrate ssDNA, were determined at ~3.0 Å resolution. Structural analyses indicated that guide RNA binding induces dimerization of the NbaSPARDA complex, while target DNA engagement disrupts this dimerization. Further propagation of the guide–target heteroduplex triggers filament formation through a checkpoint mechanism. The NbaSPARDA filament consists of a backbone formed by interlocking short Argonaute proteins, with an inner layer composed of DREN nuclease domains. Filament formation leads to tetramerization of the monomeric DREN nuclease domain, activating its collateral nuclease activity against environmental nucleic acids — a feature leveraged for molecular diagnostics. For bacteria heterologously expressing the NbaSPARDA system, defense against invading bacteriophages and plasmids relies on filament formation. Collectively, these findings illustrate the detailed working mechanism of the NbaSPARDA complex and highlight the importance of its filament formation in host defense.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"510-519"},"PeriodicalIF":25.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01100-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678022","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

Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator 一种细胞内异位调节剂对神经紧张素受体 1 的抑制作用的分子机制

IF 28.1 1区生物学

Cell Research Pub Date : 2025-03-21 DOI: 10.1038/s41422-025-01095-7

Demeng Sun, Xiang Li, Qingning Yuan, Yuanxia Wang, Pan Shi, Huanhuan Zhang, Tao Wang, Wenjing Sun, Shenglong Ling, Yuanchun Liu, Jinglin Lai, Wenqin Xie, Wanchao Yin, Lei Liu, H. Eric Xu, Changlin Tian

{"title":"Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator","authors":"Demeng Sun, Xiang Li, Qingning Yuan, Yuanxia Wang, Pan Shi, Huanhuan Zhang, Tao Wang, Wenjing Sun, Shenglong Ling, Yuanchun Liu, Jinglin Lai, Wenqin Xie, Wanchao Yin, Lei Liu, H. Eric Xu, Changlin Tian","doi":"10.1038/s41422-025-01095-7","DOIUrl":"10.1038/s41422-025-01095-7","url":null,"abstract":"Biased allosteric modulators (BAMs) of G protein-coupled receptors (GPCRs) have been at the forefront of drug discovery owing to their potential to selectively stimulate therapeutically relevant signaling and avoid on-target side effects. Although structures of GPCRs in complex with G protein or GRK in a BAM-bound state have recently been resolved, revealing that BAM can induce biased signaling by directly modulating interactions between GPCRs and these two transducers, no BAM-bound GPCR–arrestin complex structure has yet been determined, limiting our understanding of the full pharmacological profile of BAMs. Herein, we developed a chemical protein synthesis strategy to generate neurotensin receptor 1 (NTSR1) with defined hexa-phosphorylation at its C-terminus and resolved high-resolution cryo-EM structures (2.65–2.88 Å) of NTSR1 in complex with both β-arrestin1 and the BAM SBI-553. These structures revealed a unique “loop engagement” configuration of β-arrestin1 coupling to NTSR1 in the presence of SBI-553, markedly different from the typical “core engagement” configuration observed in the absence of BAMs. This configuration is characterized by the engagement of the intracellular loop 3 of NTSR1 with a cavity in the central crest of β-arrestin1, representing a previously unobserved, arrestin-selective conformation of GPCR. Our findings fill the critical knowledge gap regarding the regulation of GPCR–arrestin interactions and biased signaling by BAMs, which would advance the development of safer and more efficacious GPCR-targeted therapeutics.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 4","pages":"284-295"},"PeriodicalIF":28.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-025-01095-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672367","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

Structural basis of augmenting taurine uptake by the taurine transporter in alleviating cellular senescence 通过牛磺酸转运体增加牛磺酸摄取以减轻细胞衰老的结构基础。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-20 DOI: 10.1038/s41422-025-01090-y

Heng Zhang, Nana Cui, Xiong Ma, H. Eric Xu

引用次数: 0

Author Correction: LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer 作者更正：LKB1失活促进前列腺癌表观遗传重塑诱导的谱系可塑性和抗雄激素耐药性

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-18 DOI: 10.1038/s41422-025-01097-5

Fei Li, Pengfei Dai, Huili Shi, Yajuan Zhang, Juan He, Anuradha Gopalan, Dan Li, Yu Chen, Yarui Du, Guoliang Xu, Weiwei Yang, Chao Liang, Dong Gao

引用次数: 0

SPO11 cuts!

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-17 DOI: 10.1038/s41422-025-01093-9

Sara Hariri, Neil Hunter

引用次数: 0

New insights into how parental worms protect their offspring 关于亲代蠕虫如何保护后代的新见解。

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-14 DOI: 10.1038/s41422-025-01094-8

Chenming Zeng, Eric A. Miska

引用次数: 0

Killing cancer quickly: inducing hyper-acute rejection of patient tumors 快速杀死癌症：诱导患者肿瘤的超急性排斥反应

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-13 DOI: 10.1038/s41422-025-01099-3

Eric Bartee

引用次数: 0

Publisher Correction: Comprehensive discovery and functional characterization of the noncanonical proteome 出版者更正：非典型蛋白质组的全面发现和功能表征

IF 28.1 1区生物学

Cell Research Pub Date : 2025-03-10 DOI: 10.1038/s41422-025-01091-x

Chengyu Shi, Fangzhou Liu, Xinwan Su, Zuozhen Yang, Ying Wang, Shanshan Xie, Shaofang Xie, Qiang Sun, Yu Chen, Lingjie Sang, Manman Tan, Linyu Zhu, Kai Lei, Junhong Li, Jiecheng Yang, Zerui Gao, Meng Yu, Xinyi Wang, Junfeng Wang, Jing Chen, Wei Zhuo, Zhaoyuan Fang, Jian Liu, Qingfeng Yan, Dante Neculai, Qiming Sun, Jianzhong Shao, Weiqiang Lin, Wei Liu, Jian Chen, Liangjing Wang, Yang Liu, Xu Li, Tianhua Zhou, Aifu Lin

引用次数: 0

Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis 致癌RAS诱导由P38-ULK1-PI4KB轴介导的独特形式的非规范自噬

IF 25.9 1区生物学

Cell Research Pub Date : 2025-03-07 DOI: 10.1038/s41422-025-01085-9

Xiaojuan Wang, Shulin Li, Shiyin Lin, Yaping Han, Tong Zhan, Zhiying Huang, Juanjuan Wang, Ying Li, Haiteng Deng, Min Zhang, Du Feng, Liang Ge

{"title":"Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis","authors":"Xiaojuan Wang, Shulin Li, Shiyin Lin, Yaping Han, Tong Zhan, Zhiying Huang, Juanjuan Wang, Ying Li, Haiteng Deng, Min Zhang, Du Feng, Liang Ge","doi":"10.1038/s41422-025-01085-9","DOIUrl":"10.1038/s41422-025-01085-9","url":null,"abstract":"Cancer cells with RAS mutations exhibit enhanced autophagy, essential for their proliferation and survival, making it a potential target for therapeutic intervention. However, the regulatory differences between RAS-induced autophagy and physiological autophagy remain poorly understood, complicating the development of cancer-specific anti-autophagy treatments. In this study, we identified a form of non-canonical autophagy induced by oncogenic KRAS expression, termed RAS-induced non-canonical autophagy via ATG8ylation (RINCAA). RINCAA involves distinct autophagic factors compared to those in starvation-induced autophagy and incorporates non-autophagic components, resulting in the formation of non-canonical autophagosomes with multivesicular/multilaminar structures labeled by ATG8 family proteins (e.g., LC3 and GABARAP). We have designated these structures as RAS-induced multivesicular/multilaminar bodies of ATG8ylation (RIMMBA). A notable feature of RINCAA is the substitution of the class III PI3K in canonical autophagy with PI4KB in RINCAA. We identified a regulatory P38-ULK1-PI4KB-WIPI2 signaling cascade governing this process, where ULK1 triggers PI4KB phosphorylation at S256 and T263, initiating PI4P production, ATG8ylation, and non-canonical autophagy. Importantly, elevated PI4KB phosphorylation at S256 and T263 was observed in RAS-mutated cancer cells and colorectal cancer specimens. Inhibition of PI4KB S256 and T263 phosphorylation led to a reduction in RINCAA activity and tumor growth in both xenograft and KPC models of pancreatic cancer, suggesting that targeting ULK1-mediated PI4KB phosphorylation could represent a promising therapeutic strategy for RAS-mutated cancers.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 6","pages":"399-422"},"PeriodicalIF":25.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01085-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569557","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