Cell Proliferation最新文献_第10页

Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis HCK/谷氨酰胺/自噬轴的异常会损害巨噬细胞的吞噬功能，从而促进子宫内膜异位症的发展。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-07-02 DOI: 10.1111/cpr.13702

Sha-Ting Lei, Zhen-Zhen Lai, Shu-Hui Hou, Yu-Kai Liu, Ming-Qing Li, Dong Zhao

{"title":"Abnormal HCK/glutamine/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis","authors":"Sha-Ting Lei, Zhen-Zhen Lai, Shu-Hui Hou, Yu-Kai Liu, Ming-Qing Li, Dong Zhao","doi":"10.1111/cpr.13702","DOIUrl":"10.1111/cpr.13702","url":null,"abstract":"The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491052","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

Single-cell sequencing: Current applications in various tuberculosis specimen types 单细胞测序：目前在各种结核病标本类型中的应用。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-07-02 DOI: 10.1111/cpr.13698

Yuqin Zeng, Quan Ma, Jinyun Chen, Xingxing Kong, Zhanpeng Chen, Huazhen Liu, Lanlan Liu, Yan Qian, Xiaomin Wang, Shuihua Lu

{"title":"Single-cell sequencing: Current applications in various tuberculosis specimen types","authors":"Yuqin Zeng, Quan Ma, Jinyun Chen, Xingxing Kong, Zhanpeng Chen, Huazhen Liu, Lanlan Liu, Yan Qian, Xiaomin Wang, Shuihua Lu","doi":"10.1111/cpr.13698","DOIUrl":"10.1111/cpr.13698","url":null,"abstract":"Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (M.tb) and responsible for millions of deaths worldwide each year. It has a complex pathogenesis that primarily affects the lungs but can also impact systemic organs. In recent years, single-cell sequencing technology has been utilized to characterize the composition and proportion of immune cell subpopulations associated with the pathogenesis of TB disease since it has a high resolution that surpasses conventional techniques. This paper reviews the current use of single-cell sequencing technologies in TB research and their application in analysing specimens from various sources of TB, primarily peripheral blood and lung specimens. The focus is on how these technologies can reveal dynamic changes in immune cell subpopulations, genes and proteins during disease progression after M.tb infection. Based on the current findings, single-cell sequencing has significant potential clinical value in the field of TB research. Next, we will focus on the real-world applications of the potential targets identified through single-cell sequencing for diagnostics, therapeutics and the development of effective vaccines.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13698","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491053","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

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IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-07-01 DOI: 10.1111/cpr.13709

Fan Li, Najmeh Karimi, Siqi Wang, Tianshi Pan, Jingxi Dong, Xin Wang, Sinan Ma, Qingtong Shan, Chao Liu, Ying Zhang, Wei Li, Guihai Feng

引用次数: 0

RNA m6A modification regulates cell fate transition between pluripotent stem cells and 2-cell-like cells RNA m6A修饰调控多能干细胞和类双细胞之间的细胞命运转变。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-07-01 DOI: 10.1111/cpr.13696

Zhongqu Su, Yu Dong, Jiatong Sun, You Wu, Qingqing Wei, Yuwei Liang, Zhiyi Lin, Yujun Li, Lu Shen, Chenxiang Xi, Li Wu, Yiliang Xu, Yingdong Liu, Jiqing Yin, Hong Wang, Kerong Shi, Rongrong Le, Shaorong Gao, Xiaocui Xu

{"title":"RNA m6A modification regulates cell fate transition between pluripotent stem cells and 2-cell-like cells","authors":"Zhongqu Su, Yu Dong, Jiatong Sun, You Wu, Qingqing Wei, Yuwei Liang, Zhiyi Lin, Yujun Li, Lu Shen, Chenxiang Xi, Li Wu, Yiliang Xu, Yingdong Liu, Jiqing Yin, Hong Wang, Kerong Shi, Rongrong Le, Shaorong Gao, Xiaocui Xu","doi":"10.1111/cpr.13696","DOIUrl":"10.1111/cpr.13696","url":null,"abstract":"N6-methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal-to-zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2-cell-like (2C-like) cells remain elusive. Here, we utilised ultralow-input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome-wide m6A modifications during 2C-like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C-like cells. During the exit of the 2C-like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C-like state exit and expanding 2C-like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C-like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13696","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476030","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

Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies 探索肺腺癌上皮细胞的多样性：推进预后方法和免疫治疗策略。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-30 DOI: 10.1111/cpr.13703

Lianmin Zhang, Yanan Cui, Jie Mei, Zhenfa Zhang, Pengpeng Zhang

{"title":"Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies","authors":"Lianmin Zhang, Yanan Cui, Jie Mei, Zhenfa Zhang, Pengpeng Zhang","doi":"10.1111/cpr.13703","DOIUrl":"10.1111/cpr.13703","url":null,"abstract":"Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learning algorithms to establish a prognostic and immunotherapeutic signature (PIS) for LUAD. In multiple cohorts, PIS outperformed 144 previously published signatures in predicting LUAD prognosis. Importantly, PIS reliably predicted genomic alterations, chemotherapy sensitivity and immunotherapy responses. Immunohistochemistry validated lower expression of immune markers in the low-PIS group, while in vitro experiments underscored the role of the key gene PSMB7 in LUAD progression. In conclusion, PIS represents a novel biomarker facilitating the selection of suitable LUAD patients for immunotherapy, ultimately improving prognosis and guiding clinical decisions.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466463","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

Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin 代谢组学分析揭示了ERK在调节与格拉布林治疗的人类皮肤T细胞淋巴瘤细胞增殖相关的代谢途径中的关键作用。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-30 DOI: 10.1111/cpr.13701

Abdul Q. Khan, Maha Victor Agha, Fareed Ahmad, Rasheeda Anver, Khalid Sultan A. M. Sheikhan, Jericha Mateo, Majid Alam, Joerg Buddenkotte, Shahab Uddin, Martin Steinhoff

{"title":"Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin","authors":"Abdul Q. Khan, Maha Victor Agha, Fareed Ahmad, Rasheeda Anver, Khalid Sultan A. M. Sheikhan, Jericha Mateo, Majid Alam, Joerg Buddenkotte, Shahab Uddin, Martin Steinhoff","doi":"10.1111/cpr.13701","DOIUrl":"10.1111/cpr.13701","url":null,"abstract":"Cutaneous T-cell lymphomas (CTC) are a heterogeneous group of T-cell lymphoproliferative malignancies of the skin with limited treatment options, increased resistance and remission. Metabolic reprogramming is vital in orchestrating the uncontrolled growth and proliferation of cancer cells. Importantly, deregulated signalling plays a significant role in metabolic reprogramming. Considering the crucial role of metabolic reprogramming in cancer-cell growth and proliferation, target identification and the development of novel and multi-targeting agents are imperative. The present study explores the underlying mechanisms and metabolic signalling pathways associated with Glabridin mediated anti-cancer actions in CTCL. Our results show that Glabridin significantly inhibits the growth of CTCL cells through induction of programmed cell death (PCD) such as apoptosis, autophagy and necrosis. Interestingly, results further show that Glabridin induces PCD in CTCL cells by targeting MAPK signalling pathways, particularly the activation of ERK. Further, Glabridin also sensitized CTCL cells to the anti-cancer drug, bortezomib. Importantly, LC–MS-based metabolomics analyses further showed that Glabridin targeted multiple metabolites and metabolic pathways intricately involved in cancer cell growth and proliferation in an ERK-dependent fashion. Overall, our findings revealed that Glabridin induces PCD and attenuates the expression of regulatory proteins and metabolites involved in orchestrating the uncontrolled proliferation of CTCL cells through ERK activation. Therefore, Glabridin possesses important features of an ideal anti-cancer agent.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466464","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

Src inhibition modulates AMBRA1-mediated mitophagy to counteract endothelial-to-mesenchymal transition in renal allograft fibrosis 抑制 Src 可调节 AMBRA1 介导的有丝分裂，从而抵消肾脏异体移植纤维化过程中的内皮细胞向间质转化。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-29 DOI: 10.1111/cpr.13699

Zeping Gui, Xuzhong Liu, Zhen Xu, Dengyuan Feng, Zhou Hang, Ming Zheng, Hao Chen, Shuang Fei, Li Sun, Jun Tao, Zhijian Han, Xiaobin Ju, Min Gu, Ruoyun Tan, Zijie Wang

{"title":"Src inhibition modulates AMBRA1-mediated mitophagy to counteract endothelial-to-mesenchymal transition in renal allograft fibrosis","authors":"Zeping Gui, Xuzhong Liu, Zhen Xu, Dengyuan Feng, Zhou Hang, Ming Zheng, Hao Chen, Shuang Fei, Li Sun, Jun Tao, Zhijian Han, Xiaobin Ju, Min Gu, Ruoyun Tan, Zijie Wang","doi":"10.1111/cpr.13699","DOIUrl":"10.1111/cpr.13699","url":null,"abstract":"Chronic allograft dysfunction (CAD) poses a significant challenge in kidney transplantation, with renal vascular endothelial-to-mesenchymal transition (EndMT) playing a vital role. While renal vascular EndMT has been verified as an important contributing factor to renal allograft interstitial fibrosis/tubular atrophy in CAD patients, its underlying mechanisms remain obscure. Currently, Src activation is closely linked to organ fibrosis development. Single-cell transcriptomic analysis in clinical patients revealed that Src is a potential pivotal mediator in CAD progression. Our findings revealed a significant upregulation of Src which closely associated with EndMT in CAD patients, allogeneic kidney transplanted rats and endothelial cells lines. In vivo, Src inhibition remarkably alleviate EndMT and renal allograft interstitial fibrosis in allogeneic kidney transplanted rats. It also had a similar antifibrotic effect in two endothelial cell lines. Mechanistically, the knockout of Src resulted in an augmented AMBRA1-mediated mitophagy in endothelial cells. We demonstrate that Src knockdown upregulates AMBRA1 level and activates mitophagy by stabilizing Parkin's ubiquitination levels and mitochondrial translocation. Subsequent experiments demonstrated that the knockdown of the Parkin gene inhibited mitophagy in endothelial cells, leading to increased production of Interleukin-6, thereby inducing EndMT. Consequently, our study underscores Src as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis, exerting its impact through the regulation of AMBRA1/Parkin-mediated mitophagy.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466467","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

Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target 单细胞 RNA 测序阐明了乳腺癌脑转移灶的情况，并确定 ILF2 为潜在的治疗靶点。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-29 DOI: 10.1111/cpr.13697

Jindong Xie, Anli Yang, Qianwen Liu, Xinpei Deng, Guangzhao Lv, Xueqi Ou, Shaoquan Zheng, Min-Yi Situ, Yang Yu, Jie-Ying Liang, Yutian Zou, Hailin Tang, Zijin Zhao, Fuhua Lin, Wei Liu, Weikai Xiao

{"title":"Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target","authors":"Jindong Xie, Anli Yang, Qianwen Liu, Xinpei Deng, Guangzhao Lv, Xueqi Ou, Shaoquan Zheng, Min-Yi Situ, Yang Yu, Jie-Ying Liang, Yutian Zou, Hailin Tang, Zijin Zhao, Fuhua Lin, Wei Liu, Weikai Xiao","doi":"10.1111/cpr.13697","DOIUrl":"10.1111/cpr.13697","url":null,"abstract":"Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, the development of more efficacious strategies and the exploration of potential targets for patients with metastatic breast cancer are urgently needed. The data of six patients with breast cancer brain metastases (BCBrM) from two centres were collected, and a comprehensive landscape of the entire tumour ecosystem was generated through the utilisation of single-cell RNA sequencing. We utilised the Monocle2 and CellChat algorithms to investigate the interrelationships among each subcluster. In addition, multiple signatures were collected to evaluate key components of the subclusters through multi-omics methodologies. Finally, we elucidated common expression programs of malignant cells, and experiments were conducted in vitro and in vivo to determine the functions of interleukin enhancer-binding factor 2 (ILF2), which is a key gene in the metastasis module, in BCBrM progression. We found that subclusters in each major cell type exhibited diverse characteristics. Besides, our study indicated that ILF2 was specifically associated with BCBrM, and experimental validations further demonstrated that ILF2 deficiency hindered BCBrM progression. Our study offers novel perspectives on the heterogeneity of BCBrM and suggests that ILF2 could serve as a promising biomarker or therapeutic target for BCBrM.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466466","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

Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets tRNA 中的甲基化修饰及相关疾病：当前研究与潜在治疗目标。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-28 DOI: 10.1111/cpr.13692

Zhijing Wu, Ruixin Zhou, Baizao Li, Mingyu Cao, Wenlong Wang, Xinying Li

{"title":"Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets","authors":"Zhijing Wu, Ruixin Zhou, Baizao Li, Mingyu Cao, Wenlong Wang, Xinying Li","doi":"10.1111/cpr.13692","DOIUrl":"10.1111/cpr.13692","url":null,"abstract":"High-throughput sequencing has sparked increased research interest in RNA modifications, particularly tRNA methylation, and its connection to various diseases. However, the precise mechanisms underpinning the development of these diseases remain largely elusive. This review sheds light on the roles of several tRNA methylations (m1A, m3C, m5C, m1G, m2G, m7G, m5U, and Nm) in diverse biological functions, including metabolic processing, stability, protein interactions, and mitochondrial activities. It further outlines diseases linked to aberrant tRNA modifications, related enzymes, and potential underlying mechanisms. Moreover, disruptions in tRNA regulation and abnormalities in tRNA-derived small RNAs (tsRNAs) contribute to disease pathogenesis, highlighting their potential as biomarkers for disease diagnosis. The review also delves into the exploration of drugs development targeting tRNA methylation enzymes, emphasizing the therapeutic prospects of modulating these processes. Continued research is imperative for a comprehensive comprehension and integration of these molecular mechanisms in disease diagnosis and treatment.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466465","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

Transcription factor EB reprograms branched-chain amino acid metabolism and promotes pancreatic cancer progression via transcriptional regulation of BCAT1 转录因子 EB 通过转录调控 BCAT1 重编程支链氨基酸代谢并促进胰腺癌进展。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-27 DOI: 10.1111/cpr.13694

Ting Wang, Qiangsheng Hu, Borui Li, Guixiong Fan, Desheng Jing, Junfeng Xu, Yuheng Hu, Qin Dang, Shunrong Ji, Chenjie Zhou, Qifeng Zhuo, Xiaowu Xu, Yi Qin, Xianjun Yu, Zheng Li

{"title":"Transcription factor EB reprograms branched-chain amino acid metabolism and promotes pancreatic cancer progression via transcriptional regulation of BCAT1","authors":"Ting Wang, Qiangsheng Hu, Borui Li, Guixiong Fan, Desheng Jing, Junfeng Xu, Yuheng Hu, Qin Dang, Shunrong Ji, Chenjie Zhou, Qifeng Zhuo, Xiaowu Xu, Yi Qin, Xianjun Yu, Zheng Li","doi":"10.1111/cpr.13694","DOIUrl":"10.1111/cpr.13694","url":null,"abstract":"Pancreatic cancer cells have a much higher metabolic demand than that of normal cells. However, the abundant interstitium and lack of blood supply determine the lack of nutrients in the tumour microenvironment. Although pancreatic cancer has been reported to supply extra metabolic demand for proliferation through autophagy and other means, the specific regulatory mechanisms have not yet been elucidated. In this study, we focused on transcription factor EB (TFEB), a key factor in the regulation of autophagy, to explore its effect on the phenotype and role in the unique amino acid utilisation pattern of pancreatic cancer cells (PCCs). The results showed that TFEB, which is generally highly expressed in pancreatic cancer, promoted the proliferation and metastasis of PCCs. TFEB knockdown inhibited the proliferation and metastasis of PCCs by blocking the catabolism of branched-chain amino acids (BCAAs). Concerning the mechanism, we found that TFEB regulates the catabolism of BCAAs by regulating BCAT1, a key enzyme in BCAA metabolism. BCAA deprivation alone did not effectively inhibit PCC proliferation. However, BCAA deprivation combined with eltrombopag, a drug targeting TFEB, can play a two-pronged role in exogenous supply deprivation and endogenous utilisation blockade to inhibit the proliferation of pancreatic cancer to the greatest extent, providing a new therapeutic direction, such as targeted metabolic reprogramming of pancreatic cancer.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466468","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