Results 151 to 160 of about 201,604 (308)

NUDT21 Drives T‐Cell Acute Lymphoblastic Leukemia Through Dual Regulation of Alternative Polyadenylation and Transcriptional Activation

Advanced Science, EarlyView.
In summary, our study defines a coordinated oncogenic model in which NUDT21 integrates alternative polyadenylation–dependent UBE2D3 stabilization and transcriptional activation to sustain MYC‐driven T‐ALL cell survival, thereby establishing NUDT21 as a central regulatory node and a promising therapeutic target.
Conglian Qiu, Jianwei Wang, Zhiheng Li, Qi Ji, Hui Zhang, Qinyi Zhang, Senlin Zhang, Juanjuan Yu, Yanfang Tao, Yijun Wu, Chunxia Shi, Zong Zai, Zimu Zhang, Yizhen Li, Zhenjiang Bai, Shaoyan Hu, Jian Pan, Yang Yang, Shuiyan Wu   +18 more
wiley   +1 more source

Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G‐Quadruplex Resolution to Maintain DNA Repair and Tumor Survival

Advanced Science, EarlyView.
Glutamine deprivation triggers transient DNA damage yet activates adaptive repair in hepatocellular carcinoma cells. We identify TRIB3 as a stress‐induced nuclear scaffold that associates with DDX5 and G‐quadruplex DNA atBRCA1 andRAD51AP1 promoters. TRIB3 loss increases G4 accumulation, suppresses HR gene transcription, elevates γ‐H2A.X, and sensitizes
Qiang Ji, Xuedan Sun, Zhangran Sun, Mengfan Li, Xinyu Cheng, Shuai Tian, Rick F. Thorne, Jinming Li, Guangzhi Liu, Mian Wu, Xiaoying Liu   +10 more
wiley   +1 more source

An Activity‐Dependent NEPAS–PTX3 Axis Links Neurovascular and Myelin Deficits to Cognitive Impairment

Advanced Science, EarlyView.
An activity‐dependent pathway links prefrontal circuit hypoactivity to cognitive impairment. Reduced PVA–mPFC activity upregulates NEPAS, which suppresses PTX3 secretion, leading to impaired angiogenesis, myelin deficits, and memory decline. Rescue is achieved by NEPAS knockdown or chemogenetic circuit activation.
Boya Hu, Zifei Chen, Bingmei Sun, Jiale Gao, Jiale Xu, Xiaochun Guo, Fenfei Gao, Zhongsi Wang, Jie Wu, Xiaoyu Ji, Peipei Liu, Bing Huang   +11 more
wiley   +1 more source

Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability

Advanced Science, EarlyView.
The ER's continuous tubular network is maintained by ER‐shaping proteins whose mutation or dysregulation contributes to neurodegenerative diseases. Here, we show that ER morphology sets the speed of Ca2+ store replenishment between firing events. Disrupting ER continuity slows intra‐ER Ca2+ redistribution from extracellular refill (SOCE) sites, driving
Valentina Davi, Pierre Parutto, Yuyi Zhang, Tasuku Konno, Cecile Crapart, Raquel Pereira, John P. Franklin, Mosab Ali Awadelkareem, Daniel C Maddison, Michael J. Devine, Edgar R. Gomes, Joseph Chambers, Elena Koslover, Edward Avezov   +13 more
wiley   +1 more source

Generation of CCR4/CD7 Bispecific CAR‐T Cells Resistant to Fratricide and Exhaustion

Advanced Science, EarlyView.
The applications of CAR T‐cell therapy in T‐cell malignancies face limitations such as fratricide, effector‐cell exhaustion, and antigen‐escape. Herein, we developed fratricide‐ and exhaustion‐resistant CAR‐T cells that targeted CCR4 and CD7 simultaneously, with optional EGFRt safety switch. Additionally, scRNA‐seq unveiled new molecular targets, which
Sile Li, Yuanxin Li, Asif Rashid, Hong Kee Tan, Shing Chan, Man Yan Hui, Wilson Yau Ki Chan, Kee See Lam, Yinping Liu, Wenwei Tu, Wing Leung   +10 more
wiley   +1 more source

In Vivo CRISPR Screening Identifies the Glutamate Receptor GRIA2 as Promoting Peritoneal Metastasis of Gastric Cancer via Calcium‐Dependent β‐Catenin Activation

Advanced Science, EarlyView.
We identified GRIA2 as a critical driver of gastric cancer peritoneal metastasis through in vivo CRISPR screening. Mechanistically, GRIA2‐mediated calcium influx inhibits GSK3β and activates Wnt/β‐catenin signaling, driven by glutamate from cancer‐associated fibroblasts.
Jie Sun, Xu Yang, Wenchao Jiang, Chengbo Ji, Yingying Wu, Haoyu Sun, Xinyou Liu, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Junjie Zhao, Yuanyuan Ruan, Haojie Li, Xuefei Wang   +13 more
wiley   +1 more source

ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis

Advanced Science, EarlyView.
Zmat1 deficiency mitigates pathological bone loss by impairing osteoclastogenesis and promoting osteoblastogenesis. Mechanistically, in osteoclasts, Zmat1 loss relieves transcriptional repression of the E3 ligase TRIM46, promoting YAP1 degradation and inhibiting osteoclastogenic genes.
Xinyu Chang, Yijin Hou, Likun Cui, Huiqi Yu, Rong Liu, Junhao Sui, Zhong Zheng, Lu Liu, Jie Chen, Mengchen Chen, Chen Ding, Shuogui Xu, Sheng Xu, Hao Zhang   +13 more
wiley   +1 more source

BZW1 Drives Immune Evasion in Lung Adenocarcinoma via Ferroptosis Suppression

Advanced Science, EarlyView.
BZW1 attenuates ferroptosis by competitively binding NCOA4 and suppress ferrtinophagy‐mediated iron release. The depletion of BZW1 triggers lipid peroxidation through iron homeostasis. Extracellularly, BZW1 attenuates immunogenic cell death and reinvigorates cytotoxic T‐cell responses.
Linyao Zhao, Yue Peng, Qing Liang, Shi Liu, Yang Li, Lei Ma, Menghan Hu, Sujuan Zheng, Zhihua Liu, Shugeng Gao   +9 more
wiley   +1 more source

Promoter Hypermethylation‐Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5‐Mediated Wnt/β‐Catenin Pathway Activation

Advanced Science, EarlyView.
This study identifies FXYD1 as an epigenetically silenced tumor suppressor in breast cancer. DNA methylation turns off the gene FXYD1 in breast cancer, and low levels predict worse outcomes. Restoring FXYD1 limits breast cancer cells proliferation and metastasis. In the nucleus, FXYD1 recruits the E3 ligase MAEA to K63‐ubiquitinate DDX5 for proteasomal
Ping Wen, Fanli Qu, Long Wang, Qing Shao, Sisi Li, Yang Qin, Dongping Jiang, Senmiao Zhang, Jiangdong Sui, Guanwen Wang, Ningning Zhang, Xiaohua Zeng   +11 more
wiley   +1 more source

Enhancing CAR‐T Cell Efficacy in Solid Tumors by Inhibiting CCL5/VEGF‐Mediated Angiogenesis

Advanced Science, EarlyView.
This study reveals that CAR‐T cells in solid tumors produce CCL5, which paradoxically induces VEGF and angiogenesis to promote tumor growth. Blocking CCL5/VEGF signaling—through gene knockout, or the CCR5 inhibitor maraviroc—significantly enhances the antitumor efficacy of CAR‑T therapy (the diagram was created in Biorender).
Shishuo Sun, Qihong Li, Bixi Wang, Gang Wang, Ying Xue, Yibing Liang, Chenhe Hu, Zhenyu Wang, Xiaoge Gao, Haiheng Xu, Jun Song, Hailong Li, Liantao Li, Xiaoxiao Liu, Patrick Ming‐Kuen Tang, Qing Zhang   +15 more
wiley   +1 more source