Article Biochemistry & Molecular Biology
Hippocampal BMP signaling as a common pathway for antidepressant action
Elif Tunc-Ozcan, Sarah M. Brooker, Jacqueline A. Bonds, Yung-Hsu Tsai, Radhika Rawat, Tammy L. McGuire, Chian-Yu Peng, John A. Kessler
Summary: Hippocampal BMP signaling is identified as a common pathway mediating the behavioral effects of multiple antidepressant classes and electroconvulsive therapy. Inhibition of hippocampal BMP signaling is shown to be both necessary and sufficient to mediate the effects of these treatments, involving a key role in neurogenesis in the hippocampus.
CELLULAR AND MOLECULAR LIFE SCIENCES (2022)
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Article Biology
GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway
Virginia Kroef, Sabine Ruegenberg, Moritz Horn, Kira Allmeroth, Lena Ebert, Seyma Bozkus, Stephan Miethe, Ulrich Elling, Bernhard Schermer, Ulrich Baumann, Martin Sebastian Denzel
Summary: The hexosamine biosynthetic pathway (HBP) is crucial in metabolism, health, and aging as it produces UDP-GlcNAc. In addition to the known regulation by GFPT, a new regulator, AMDHD2, has been identified that modulates the HBP by its loss leading to increased UDP-GlcNAc levels and HBP activation.
ELIFE (2022)
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Review Genetics & Heredity
SMAD6-deficiency in human genetic disorders
Ilse Luyckx, Aline Verstraeten, Marie-Jose Goumans, Bart Loeys
Summary: This article reviews the clinical and genetic similarities of three diseases related to SMAD6, compares mouse models, and discusses the cellular mechanisms of SMAD6 in the development of these diseases. The importance of further research to improve molecular diagnosis, advance therapeutic strategies, and provide counseling for patients and their families is also emphasized.
NPJ GENOMIC MEDICINE (2022)
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Article Peripheral Vascular Disease
SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis
Dana L. Ruter, Ziqing Liu, Kimlynn M. Ngo, X. Shaka, Allison Marvin, Danielle B. Buglak, Elise J. Kidder, Victoria L. Bautch
Summary: Fluid shear stress from blood flow triggers a transition from active blood vessel expansion to vascular homeostasis, with SMAD6 playing a crucial role in maintaining this balance. SMAD6 functions downstream of Notch signaling and transcription regulation, rescuing flow misalignment induced by Notch loss. Upregulation of PCDH12 by SMAD6 is required for proper endothelial cell alignment in response to flow, placing SMAD6 as a key mediator between Notch1 and PCDH12 during this transition in vessel phenotype.
ANGIOGENESIS (2021)
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Article Chemistry, Multidisciplinary
Engineered Sensory Nerve Guides Self-Adaptive Bone Healing via NGF-TrkA Signaling Pathway
Zengjie Zhang, Fangqian Wang, Xin Huang, Hangxiang Sun, Jianxiang Xu, Hao Qu, Xiaobo Yan, Wei Shi, Wangsiyuan Teng, Xiaoqiang Jin, Zhenxuan Shao, Yongxing Zhang, Shenzhi Zhao, Yan Wu, Zhaoming Ye, Xiaohua Yu
Summary: The role of sensory innervation in bone homeostasis is often overlooked in bone repair strategies. This study proposes a neuromodulation approach that uses engineered sensory nerves (eSN) to optimize bone defect healing by leveraging the adaptive capabilities of sensory neurons. The release of NGF from ECM-constructed eSN promotes sensory neuron differentiation and enhances CGRP secretion, leading to improved mobility of RAOECs and osteogenic differentiation of BMSCs. The eSN approach effectively drives ossification in vivo through the NGF-TrkA signaling pathway, accelerating the healing of critical size bone defects. It also suppresses excessive bone formation and promotes bone remodeling by activating osteoclasts via a CGRP-dependent mechanism when combined with BMP-2 delivery, mitigating the side effects of BMP-2. Overall, this eSN approach offers a valuable avenue for optimizing bone homeostasis in various clinical scenarios by harnessing the adaptive role of the neural system.
ADVANCED SCIENCE (2023)
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Article Medicine, Research & Experimental
Ataluren prevented bone loss induced by ovariectomy and aging in mice through the BMP-SMAD signaling pathway
Lijun Zeng, Ranli Gu, Wei Li, Yuzi Shao, Yuan Zhu, Zhengwei Xie, Hao Liu, Yongsheng Zhou
Summary: Both estrogen deficiency and aging can cause osteoporosis. Developing new drugs for treating osteoporosis is a popular research direction. Through deep learning-based efficacy prediction system (DLEPS), potential therapeutic agents were screened and ataluren was identified as a potential drug for treating osteoporosis. Ataluren reversed bone loss and promoted osteogenic differentiation in animal and cell models.
BIOMEDICINE & PHARMACOTHERAPY (2023)
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Article Pharmacology & Pharmacy
BMP-7 Upregulates Id2 Through the MAPK Signaling Pathway to Improve Diabetic Tubulointerstitial Fibrosis and the Intervention of Oxymatrine
Yawen Xiao, Dan Liang, Zhiyang Li, Zhaowei Feng, Zhiping Yuan, Fan Zhang, Yuanyuan Wang, Yuxia Zhou, Mingjun Shi, Lingling Liu, Ying Xiao, Bing Guo
Summary: BMP-7 improves diabetic nephropathy by inhibiting MAPK pathway phosphorylation and upregulating Id2 protein expression. Oxymatrine ameliorates early epithelial-to-mesenchymal transition in diabetic kidney disease by regulating the BMP-7-MAPK pathway.
FRONTIERS IN PHARMACOLOGY (2022)
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Article Developmental Biology
Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development
Molly R. Kulikauskas, Morgan Oatley, Tianji Yu, Ziqing Liu, Lauren Matsumura, Elise Kidder, Dana Ruter, Victoria L. Bautch
Summary: SMAD6 functions as a negative regulator of ALK1-mediated responses in endothelial cells, and its loss increases signaling through ALK1, disrupting endothelial cell junctions. Loss of ALK1 function also disrupts vascular development and function.
DEVELOPMENT (2023)
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Review Pharmacology & Pharmacy
A review of BMP and Wnt signaling pathway in the pathogenesis of pulmonary arterial hypertension
Zhihong Xin, Junfu Wang, Susu Li, Chao Sun, Wan Jiang, Qian Xin, Jue Wang, Tonggnag Qi, Kailin Li, Zhaohua Zhang, Yun Luan
Summary: Pulmonary arterial hypertension (PAH) is a chronic disease characterized by elevated mean pulmonary arterial pressure leading to right heart failure and death. Current therapeutic options are limited, but restoration of BMPR2 signaling pathway shows promise in preventing and reversing pulmonary vascular remodeling in PAH.
CLINICAL AND EXPERIMENTAL HYPERTENSION (2022)
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Article Biochemistry & Molecular Biology
Arginine methylation of R81 in Smad6 confines BMP-induced Smad1 signaling
Jian Wu, Xi Chen, Prerna Sehgal, Tingwei Zhang, Olan Jackson-Weaver, Yongchao Gou, Victoria Bautch, Baruch Frenkel, Hongchen Sun, Jian Xu
Summary: Bone morphogenetic proteins (BMPs) secreted by various cell types are crucial for cell differentiation and matrix formation. BMPs activate intracellular effectors via phosphorylation of Smad1, Smad5, and Smad9, with Smad6 inhibiting BMP signaling through various mechanisms. This study reveals a cytosolic mechanism of Smad6 action involving arginine methylation at R81, which interferes with Smad1-Smad4 complex formation and attenuates BMP responses.
JOURNAL OF BIOLOGICAL CHEMISTRY (2021)
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Article Multidisciplinary Sciences
SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/I & kappa;B/p65 signaling pathway
Yiwen Ma, Jiateng Hu, Xingjuan Xue, Jianmin Gu, Yuyan Pan, Jun Yang
Summary: Macrophages preferentially polarize to M2 subtype in wound microenvironment. SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through suppression of inflammation, promotion of angiogenesis, and collagen remodeling. Mechanistically, SENP3 knockout facilitates M2 polarization via the Smad6/IκB/p65 signaling pathway.
HELIYON (2023)
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Review Biotechnology & Applied Microbiology
Improving bone morphogenetic protein (BMP) production in CHO cells through understanding of BMP synthesis, signaling and endocytosis
Kyungsoo Kim, Mi Gyeom Kim, Gyun Min Lee
Summary: Bone morphogenetic proteins (BMPs) are growth factors with potential in clinical applications for regulating bone and cartilage formation. Producing recombinant human BMPs (rhBMPs) in Chinese hamster ovary (CHO) cells is challenging due to their maturation processes, signaling pathways, and endocytosis. Understanding the properties of individual rhBMPs is crucial for enhancing their production in CHO cells.
BIOTECHNOLOGY ADVANCES (2023)
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Article Oncology
Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma
Kiyotaka Yokogami, Takashi Watanabe, Shinji Yamashita, Asako Mizuguchi, Hideo Takeshima
Summary: The aim of this paper is to find the therapeutic target of meningiomas. The method is to study the effects of BMP signal inhibitors and Gremlin2 on the growth and senescence of meningiomas. The results show that the inhibition of BMP receptor and the forced expression of GREM2 can change tryptophan metabolism, reduce the production of NAD+/NADH, decrease the expression of gene clusters involved in oxidative phosphorylation, and lead to a decrease in ATP. Finally, malignant meningiomas undergo cellular senescence, proliferation is reduced, and psammoma bodies are eventually formed. The conclusion is that the GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.
JOURNAL OF NEURO-ONCOLOGY (2024)
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Article Agriculture, Dairy & Animal Science
Characterization of Growth Secondary Hair in Min Pig Activated by Follicle Stem Cell Stimulated by Wnt and BMP Signaling Pathway
Xinmiao He, Ziliang Qin, Ran Teng, Ming Tian, Wentao Wang, Yanzhong Feng, Heshu Chen, Haijuan He, Haifeng Zhang, Di Liu, Xinpeng Jiang
Summary: The Min pig, a national-level protected pig in China, has unique characteristics compared to other commercial pigs. In this study, the structure and gene expression of hair follicles in Min pigs were analyzed, and it was found that Wnt and BMP signaling pathways can stimulate follicle stem cells in Min pigs.
ANIMALS (2023)
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Review Cell Biology
BMP Signaling Pathway in Dentin Development and Diseases
Mengmeng Liu, Graham Goldman, Mary MacDougall, Shuo Chen
Summary: BMP signaling plays a crucial role in dentin development, regulating the differentiation and gene expression of odontoblasts through canonical and non-canonical Smad signaling pathways. Dysregulation of BMP signaling leads to tooth disorders, and studies in mice with BMP signaling-associated gene mutations or knockouts have provided insights into the underlying networks. This review summarizes recent advances in understanding BMP signaling in odontoblast differentiation and dentin formation, including the expression of BMPs, receptors, and downstream genes, as well as the structures of BMPs, receptors, antagonists, and their association with dentin defects.
CELLS (2022)
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Review Biology
Permafrost carbon cycle and its dynamics on the Tibetan Plateau
Leiyi Chen, Guibiao Yang, Yuxuan Bai, Jinfeng Chang, Shuqi Qin, Futing Liu, Mei He, Yutong Song, Fan Zhang, Josep Penuelas, Biao Zhu, Guoying Zhou, Yuanhe Yang
Summary: The study focuses on the permafrost carbon cycle in the Tibetan Plateau. It summarizes the recent progress, including the stocks and fluxes of permafrost carbon and their responses to thawing. The article also discusses the impact of permafrost thaw on carbon mobilization and the importance of the region as a carbon sink. Finally, it suggests future research directions, such as developing long-term observation networks and improving model projections.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Review Biology
Biomolecular condensates and disease pathogenesis
Ruan Ke, Bai Ge, Yanshan Fang, Li Dan, Tingting Li, Xingguo Liu, Boxun Lu, Lu Qing, Songyang Zhou, Shuguo Sun, Wang Zheng, Zhang Xin, Zhou Wen, Zhang Hong
Summary: This article introduces biomolecular condensates or membraneless organelles formed by liquid-liquid phase separation, whose dysfunction is associated with a variety of diseases. The article also summarizes the progress in monitoring phase separation methods, discusses the formation and function of MLOs, and presents examples of disrupted phase separation homeostasis, and finally describes the discovery of chemical modulators of phase separation.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Conservation genomics of the critically endangered Chinese pangolin
Shichao Wei, Huizhong Fan, Wenliang Zhou, Guangping Huang, Yan Hua, Shibao Wu, Xiao Wei, Yiting Chen, Xinyue Tan, Fuwen Wei
Summary: This study analyzed the genomes of three subspecies of the Chinese pangolin, revealing its population structure, evolutionary history, and adaptive potential. It was found that past climate change led to population differentiation, while recent human activities have had a negative impact on some populations. Some populations are at risk of extinction and require conservation measures, such as strengthening habitat management and conducting genetic rescue. This study provides important scientific basis for the conservation of the Chinese pangolin.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Decoding the biochemical dialogue: metabolomic insights into soybean defense strategies against diverse pathogens
Min Qiu, Mengjun Tian, Yaru Sun, Huaibo Li, Wenwen Huang, Haibing Ouyang, Shaoyan Lin, Chen Zhang, Ming Wang, Yuanchao Wang
Summary: This study analyzed the interaction between soybeans and five pathogens using LC-MS technology, identifying 627 spectra and four main modules. After infection, changes occurred in the primary and secondary metabolism of soybeans, with bidirectional changes in total flavonoids and a general decline in triterpenoids. The study also explored the biological roles of five compounds, finding that they have multiple functions against pathogens, such as inhibiting vegetative growth and virulence. This study emphasizes the powerful utility of metabolomic tools and provides strategic approaches for enhancing plant resistance to diseases.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Ethical concerns in aging research: perspectives of global frontline researchers
Yaojin Peng, Lulu Ding, Zhenyu Xiao, Moshi Song, Jianwei Lv, Guang-Hui Liu
Summary: This study investigated the ethical landscape of aging research in the context of the growing global focus on extending human lifespan and healthspan. The survey revealed differences in perceptions of aging, consensus on the feasibility of delaying aging, and multiple perspectives on lifespan extension. The findings emphasize the need for a paradigm shift towards inclusive and ethically sound research, as well as highlight key ethical concerns in aging research, including the impact of misleading advertising, potential inequality in access to aging interventions, and risks associated with extrapolating research findings from lower-model organisms to humans. The insights presented in this paper call for an integrated approach to overcome the complex ethical and social challenges in aging research.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Review Biology
CRISPR beyond: harnessing compact RNA-guided endonucleases for enhanced genome editing
Feizuo Wang, Shengsheng Ma, Senfeng Zhang, Quanquan Ji, Chunyi Hu
Summary: The CRISPR-Cas system is useful for genome editing, but the large size of traditional CRISPR-Cas effectors makes it difficult to deliver them effectively to organisms and cells. Therefore, the development of compact and miniature gene editors is necessary. The article introduces two development strategies and emphasizes the progress and potential of miniature genome editors.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Combined effects of climate and land-use changes on the alpha and beta functional diversities of terrestrial mammals in China
Chao Zhang, Yumei Li, Wei Wang, Zexuan Gao, Hanqing Liu, Yonggang Nie
Summary: Climate and land-use changes impact biodiversity. This study investigated their potential effects on the functional diversity of terrestrial mammals in China. Findings showed a positive correlation between functional and species richness, and that functional evenness, specialization, and originality decreased with species richness. Under low-emission scenarios, land-use change had a greater impact on species richness, while under high-emission scenarios, climate change had a greater impact. Functional richness changed differently from species richness, and mammal assemblages showed potential functional differentiation.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
LPS-related muscle loss is associated with the alteration of Bacteroidetes abundance, systemic inflammation, and mitochondrial morphology in a weaned piglet model
Jiayi Yu, Changbing Zheng, Qiuping Guo, Yulong Yin, Yehui Duan, Fengna Li
Summary: This study shows that LPS-induced immune stress causes a decrease in muscle mass in piglets, which is related to a reduction in the abundance of Bacteroidetes, an increase in inflammation, and the disruption of mitochondrial morphology. In addition, oral administration of rhIL-6 can induce the overexpression of inflammatory cytokines, resulting in a decrease in muscle mass, while pretreatment with Mdivi-1 can alleviate LPS-induced muscle mass loss. These findings provide potential therapeutic targets for reducing muscle mass loss.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Review Biology
Suppressor tRNA in gene therapy
Jingjing Ruan, Xiaoxiao Yu, Huixia Xu, Wenrui Cui, Kaiye Zhang, Chenyang Liu, Wenlong Sun, Xiaodan Huang, Lei An, Yue Zhang
Summary: This article introduces the mechanism and development of suppressor tRNA in gene therapy, compares its advantages and disadvantages with other readthrough therapies, and discusses its application prospects, limitations, and obstacles in clinical therapy. It also summarizes the applications of suppressor tRNA in vitro and in vivo, providing new ideas for the research and treatment of nonsense mutation diseases.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Single-cell immune landscape of measurable residual disease in acute myeloid leukemia
Xiaodong Mo, Weilong Zhang, Guomei Fu, Yingjun Chang, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Mengzhu Shen, Qiuxia Wei, Changjian Yan, Xiaojun Huang
Summary: This study analyzed bone marrow samples from MRD-positive and -negative patients using single-cell RNA sequencing, revealing the characteristics of the immune cell landscape, including differences in the expression levels of cytotoxicity-related genes, the enrichment of specific cell clusters, and the interactions between cell clusters. These findings contribute to a better understanding of the immune mechanisms underlying MRD conversion.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy
Peidong Zhang, Peiwei Li, Muya Tang, Ryan C. Gimple, Liang Huang, Jing Yue, Qiuhong Shen, Yiwei Du, Qian Zhang, Zhengnan Yang, Haihuai He, Kailin Yang, Linjie Zhao, Shengtao Zhou
Summary: This study used the TCGA database to profile alterations in mechanotransduction pathway genes across 31 cancer types and classified them into 6 subtypes. Each subtype has a unique molecular expression pattern, mutational landscape, immune infiltration, and clinical outcome. The study also found that different subtypes of cancer respond differently to mechanotherapeutic agents, suggesting that the cancer stratification system can predict patient responses to mechanotherapy. This study provides a novel pan-cancer landscape of mechanotransduction pathways and highlights its potential clinical significance in cancer treatment.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects
Mengting Wang, Liping Wang, Yanxin Huang, Zhibin Qiao, Shanru Yi, Weina Zhang, Jing Wang, Guang Yang, Xinyu Cui, Xiaochen Kou, Yanhong Zhao, Hong Wang, Cizhong Jiang, Shaorong Gao, Jiayu Chen
Summary: This study successfully generated mice with catalytically inactive specific Tet members, and compared with knockout mice, mutant mice showed significant developmental defects. The study also found that Tet3 had a significant impact on the global hydroxymethylation, gene expression, and differentiation potential of mESCs, and there were common regulatory regions between Tet1 and Tet3 in pluripotency regulation. This study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
Reevaluation by the CRISPR/Cas9 knockout approach revealed that multiple pluripotency-associated lncRNAs are dispensable for pluripotency maintenance while Snora73a/b is essential for pluripotency exit
Zhen Li, Xuefei Li, Jingxia Lin, Yangming Wang, Huiqing Cao, Jiajian Zhou
Summary: This study knocked out 8 lncRNAs that were thought to promote pluripotency in mouse embryonic stem cells using CRISPR/Cas9 technology, and found that they were not essential. Single-cell transcriptomic analysis showed that these lncRNAs had little impact on pluripotency gene expression and cell identity. In addition, the study also found that some shRNAs used to knockdown lncRNAs caused the downregulation of pluripotency genes, which may be due to off-target effects. Interestingly, linc1343 knockout ESCs showed high expression of pluripotency genes and failed to form cystic structures during differentiation, and the reintroduction of two snoRNAs from the RNA products generated by the linc1343 locus could rescue this defect. These results suggest that these lncRNAs may not have important functions in conventional ESC culture, and snoRNAs may play a key role in pluripotency gene silencing.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells
Weixiao Yan, Xiaotong Wang, Wenjing Wang, Qi Guo, Na Huang, Hao Chen, Xing-Jie Liang, Yu Han, Dandan Liu, Jinchao Zhang
Summary: This study reveals the crucial role of the p38/MAPK signaling pathway in regulating the motility and metastasis of therapy-escape cancer stem cells (TSCSC), and proposes a therapeutic strategy targeting TSCSC.
SCIENCE CHINA-LIFE SCIENCES (2024)
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Article Biology
The repression of oncoprotein SET by the tumor suppressor p53 reveals a p53-SET-PP2A feedback loop for cancer therapy
Han Yao, Wenbin Xu, Yajing Liu, Zhijie Cao, Jia Wen, Mi Zhang, Zhen Wu, Xiaojun Yan, Zishan Jiao, Zijing Zhang, Jianyuan Chen, Meng Zhang, Wei-Guo Zhu, Donglai Wang
Summary: The oncoprotein SET contributes to malignant tumors through multiple mechanisms, and its regulation in cancer cells is not well understood. This study reveals that the tumor suppressor p53 transcriptionally represses SET expression and stimulates PP2A phosphatase activity. The interaction between SET and PP2A can be targeted to enhance p53 activation and achieve synergistic tumor suppression. These findings provide mechanistic insights and a potential strategy for cancer therapy.
SCIENCE CHINA-LIFE SCIENCES (2023)
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