Cell ResearchPub Date : 2025-05-16DOI: 10.1038/s41422-025-01130-7
Liushuai Li, Yajie Liu, Juhong Rao, Hengrui Hu, Jia Liu, Xi Wang, Jiang Li, Zhihong Hu, Manli Wang
{"title":"Mucin-like protein of Crimean-Congo hemorrhagic fever virus is a key virulence factor and a potent target for developing novel attenuated vaccine","authors":"Liushuai Li, Yajie Liu, Juhong Rao, Hengrui Hu, Jia Liu, Xi Wang, Jiang Li, Zhihong Hu, Manli Wang","doi":"10.1038/s41422-025-01130-7","DOIUrl":"10.1038/s41422-025-01130-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"524-527"},"PeriodicalIF":25.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065801","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}
Cell ResearchPub Date : 2025-05-14DOI: 10.1038/s41422-025-01125-4
Pan Geng, Changxuan Li, Xuebo Quan, Jiaxuan Peng, Zhiying Yao, Yunhe Wang, Ming Yang, Yanning Wang, Yunfan Jin, Yan Xiong, Hongtao Liu, Yijun Qi, Peiguo Yang, Kai Huang, Xiaofeng Fang
{"title":"A thermosensor FUST1 primes heat-induced stress granule formation via biomolecular condensation in Arabidopsis","authors":"Pan Geng, Changxuan Li, Xuebo Quan, Jiaxuan Peng, Zhiying Yao, Yunhe Wang, Ming Yang, Yanning Wang, Yunfan Jin, Yan Xiong, Hongtao Liu, Yijun Qi, Peiguo Yang, Kai Huang, Xiaofeng Fang","doi":"10.1038/s41422-025-01125-4","DOIUrl":"10.1038/s41422-025-01125-4","url":null,"abstract":"The ability to sense cellular temperature and induce physiological changes is pivotal for plants to cope with warming climate. Biomolecular condensation is emerging as a thermo-sensing mechanism, but the underlying molecular basis remains elusive. Here we show that an intrinsically disordered protein FUST1 senses heat via its condensation in Arabidopsis thaliana. Heat-dependent condensation of FUST1 is primarily determined by its prion-like domain (PrLD). All-atom molecular dynamics simulation and experimental validation reveal that PrLD encodes a thermo-switch, experiencing lock-to-open conformational changes that control the intermolecular contacts. FUST1 interacts with integral stress granule (SG) components and localizes in the SGs. Importantly, FUST1 condensation is autonomous and precedes condensation of several known SG markers and is indispensable for SG assembly. Loss of FUST1 significantly delays SG assembly and impairs both basal and acquired heat tolerance. These findings illuminate the molecular basis for thermo-sensing by biomolecular condensation and shed light on the molecular mechanism of heat stress granule assembly.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"483-496"},"PeriodicalIF":25.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01125-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945476","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}
{"title":"DNA remnants in red blood cells enable early detection of cancer","authors":"Haobo Sun, Xingyun Yao, Yurong Jiao, Xiangxing Kong, Yuehua Han, Ying Li, Jianping Ge, Yanfei Cao, Hongsheng Lu, Pingli Wang, Yu Xu, Jun Li, Kefeng Ding, Xiaofei Gao","doi":"10.1038/s41422-025-01122-7","DOIUrl":"10.1038/s41422-025-01122-7","url":null,"abstract":"Cytoplasmic DNA emerges as a consequence of genomic instability. However, its potential role in disease diagnosis has yet to be fully explored. Here we analyzed DNA remnants in mature red blood cells (rbcDNA) from both healthy individuals and cancer patients. Our study unveiled distinct genomic profiles in rbcDNA from cancer patients with early-stage solid tumors compared to those of healthy donors. Significant changes in read counts at specific genomic regions within rbcDNA were identified in patients, which were termed tumor-associated rbcDNA features. These features demonstrated potential for highly accurate early-stage cancer detection, proposing a novel approach for cancer detection. Moreover, tumor-associated rbcDNA features were observed in tumor mouse models, with some features being conserved between mice and humans. Chronic, but not transient, up-regulation of interleukin-18 is essential for the development of these features by promoting DNA damage in bone marrow hematopoietic cells through the up-regulation of NR4A1. These results underscore the remote regulation of chromosomal stability in hematopoietic cells by solid tumors and propose tumor-associated rbcDNA features as a promising strategy for early cancer detection.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 8","pages":"568-587"},"PeriodicalIF":25.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926856","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}
Cell ResearchPub Date : 2025-05-07DOI: 10.1038/s41422-025-01126-3
Tao Hou, Peiqiang Yan, Hiroyuki Inuzuka, Wenyi Wei
{"title":"Lysosomal EGFR functions as a GEF for Rheb","authors":"Tao Hou, Peiqiang Yan, Hiroyuki Inuzuka, Wenyi Wei","doi":"10.1038/s41422-025-01126-3","DOIUrl":"10.1038/s41422-025-01126-3","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"475-476"},"PeriodicalIF":25.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01126-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915595","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}
Cell ResearchPub Date : 2025-05-07DOI: 10.1038/s41422-025-01124-5
Carmen Mota Reyes, Helmut Friess, Ihsan Ekin Demir
{"title":"Neural crossroads of pancreatic cancer: how nociceptors drive tumor progression and immune evasion","authors":"Carmen Mota Reyes, Helmut Friess, Ihsan Ekin Demir","doi":"10.1038/s41422-025-01124-5","DOIUrl":"10.1038/s41422-025-01124-5","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 6","pages":"393-394"},"PeriodicalIF":25.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01124-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915669","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}
Cell ResearchPub Date : 2025-04-21DOI: 10.1038/s41422-025-01110-x
Xiaobo He, Qiu-Xia Wang, Denghui Wei, Yujie Lin, Xia Zhang, Yuanzhong Wu, Xuexia Qian, Zhihao Lin, Beibei Xiao, Qinxue Wu, Zhen Wang, Fengtao Zhou, Zhihao Wei, Jingxuan Wang, Run Gong, Ruhua Zhang, Qingling Zhang, Ke Ding, Song Gao, Tiebang Kang
{"title":"Lysosomal EGFR acts as a Rheb-GEF independent of its kinase activity to activate mTORC1","authors":"Xiaobo He, Qiu-Xia Wang, Denghui Wei, Yujie Lin, Xia Zhang, Yuanzhong Wu, Xuexia Qian, Zhihao Lin, Beibei Xiao, Qinxue Wu, Zhen Wang, Fengtao Zhou, Zhihao Wei, Jingxuan Wang, Run Gong, Ruhua Zhang, Qingling Zhang, Ke Ding, Song Gao, Tiebang Kang","doi":"10.1038/s41422-025-01110-x","DOIUrl":"10.1038/s41422-025-01110-x","url":null,"abstract":"Oncogenic mutations in EGFR often result in EGF-independent constitutive activation and aberrant trafficking and are associated with several human malignancies, including non-small cell lung cancer. A major consequence of EGFR mutations is the activation of the mechanistic target of rapamycin complex 1 (mTORC1), which requires EGFR kinase activity and downstream PI3K/AKT signaling, resulting in increased cell proliferation. However, recent studies have elucidated kinase-independent roles of EGFR in cell survival and cancer progression. Here, we report a cis mTORC1 activation function of EGFR that is independent of its kinase activity. Our results reveal that lysosomal localization of EGFR is critical to mTORC1 activation, where EGFR physically binds Rheb, acting as a guanine exchange factor (GEF) for Rheb, with its Glu804 serving as a potential glutamic finger. Genetic knock-in of EGFR-E804K in cells reduces the level of GTP-bound Rheb, and significantly suppresses mTORC1 activation, cell proliferation and tumor growth. Different tyrosine kinase inhibitors exhibit distinct effects on EGFR-induced mTORC1 activation, with afatinib, which additionally blocks EGFR’s GEF activity, causing a much greater suppression of mTORC1 activation and cell growth, and erlotinib, which targets only kinase activity, resulting in only a slight decrease. Moreover, a novel small molecule, BIEGi-1, was designed to target both the Rheb-GEF and kinase activities of EGFR, and shows a strong inhibitory effect on the viability of cells harboring EGFR mutants. These findings unveil a fundamental event in cell growth and suggest a promising strategy against cancers with EGFR mutations.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 7","pages":"497-509"},"PeriodicalIF":25.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01110-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853179","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}