Results 61 to 70 of about 3,370 (187)

Targeting WDR12 Unleashes T‐Cell‐Mediated Antitumor Activity in Melanoma by Destabilizing CD276

Advanced Science, EarlyView.
WDR12 cooperates with the chaperonin subunit CCT7 to maintain CD276 stability on tumor cells, suppressing T‐cell activity and promoting immune escape. SU14813, a small‐molecule WDR12 inhibitor, reduces CD276 stability and relieves CD276‐mediated T‐cell suppression.
Jie Pan, Ruimin Chang, Meng Zhang, Qian Dong, Guanxiong Zhang, Xiang Chen, Mingliang Chen, Lixia Lu, Xiaowei Liang, Yeye Guo, Juan Su   +10 more
wiley   +1 more source

Functional Suppression of SCAP Triggers Endoplasmic Reticulum Stress‐Dependent Ferroptosis by Impairing Cholesterol Metabolism in Gastric Cancer

Advanced Science, EarlyView.
This study reveals a novel GC therapy targeting cholesterol homeostasis. Inhibiting the SCAP sterol‐sensing domain causes lethal ER stress via cholesterol accumulation, paradoxically forcing continuous synthesis that triggers ferroptosis. The findings link sterol sensing, metabolic dysregulation, and ferroptosis, establishing an anti‐cancer paradigm ...
Qianqian Xu, Guangzhao Pan, Lele Zhang, Xiangliu Chen, Kui Zhang, Yang Lu, Zibo Duan, Aiping Chen, Hailong Shen, Yuxi Zhang, Xiaowu Dong, Jinzhou Huang, Xing Huang, Kai Miao, Qian Hua, Fangfang Tao, Weidong Zhang, Jiang‐Jiang Qin   +17 more
wiley   +1 more source

New use for CETSA: monitoring innate immune receptor stability via post-translational modification by OGT [PDF]

Journal of Bioenergetics and Biomembranes, 2018
O-GlcNAcylation is a dynamic and functionally diverse post-translational modification shown to affect thousands of proteins, including the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (Nod2). Mutations of Nod2 (R702W, G908R and 1007 fs) are associated with Crohn's disease and have lower stabilities compared to ...
Walter R, Drake, Ching-Wen, Hou, Natasha E, Zachara, Catherine Leimkuhler, Grimes   +3 more
openaire   +2 more sources

Aldehyde Dehydrogenase 2 (ALDH2): A novel sorafenib target in hepatocellular carcinoma unraveled by the proteome-wide cellular thermal shift assay

SLAS Discovery
Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete.
Inês C. Ferreira, Estefania Torrejón, Bernardo Abecasis, Bruno M. Alexandre, Ricardo A. Gomes, Chris Verslype, Jos van Pelt, Ana Barbas, Daniel Simão, Tiago M. Bandeiras, Alessio Bortoluzzi, Sofia P. Rebelo   +11 more
doaj   +1 more source

Targeted Delivery of Indole‐3‐Pyruvic Acid Suppresses Macrophage Ferroptosis to Enhance CD8+ T Cell‐Mediated Immunotherapy Response in Bladder Cancer

Advanced Science, EarlyView.
A microbiota‐derived metabolite, indole‐3‐pyruvic acid, suppresses macrophage ferroptosis through the AHR–NF‐κB–SLC7A11 axis. This preserves CD8+ T cell function in bladder cancer. Macrophage‐targeted nanoparticles enhance indole‐3‐pyruvic acid delivery and overcome resistance to PD‐1 blockade.
Jianwen Lao, Xinhao Yuan, Shuai Liang, Kai Deng, Daqin Wu, Longhao Xu, Kun Zheng, Yi Lin, Peicong Cai, Haoran Zheng, Junyu Chen, Mingli Luo, Yan Chen, Xiong Chen, Chunhui Wang, Wenlong Zhong   +15 more
wiley   +1 more source

Penfluridol Triggers GSDME‐Mediated Immunogenic Pyroptosis to Potentiate Antitumor Immunotherapy

Advanced Science, EarlyView.
A high‐throughput screen of FDA‐approved antipsychotics identifies penfluridol as a potent pyroptosis inducer acting via direct TTI1 inhibition. This triggers TNFA‐NFKB signaling and caspase‐8/‐3‐dependent GSDME cleavage. The compound stimulates antitumor immunity alone and synergizes with anti‐PD‐1 therapy, while low TTI1 expression emerges as a ...
Linfeng Li, Daishi Li, Danyao Chen, Yating Dian, Lei Yao, Hui Su, Ziyu Guo, Deze Zhao, Zihua Wu, Furong Zeng, Chunfang Zhang, Guangtong Deng   +11 more
wiley   +1 more source

Pyrazole‐Derived Antibacterial Compounds Effectively Treat Methicillin‐Resistant Staphylococcus Aureus Infections by Inhibiting Aspartate Transcarbamoylase

Advanced Science, EarlyView.
This study unveils a novel antibacterial mechanism against MRSA, in which the compound Py‐27 selectively targets and inhibits aspartate transcarbamoylase (ATCase), a key enzyme in pyrimidine synthesis. This inhibition disrupts DNA replication, induces oxidative damage, leading to potent bactericidal activity.
Xiaorong Yang, Xinyuan Cao, Lixia Dai, Feng Yang, Jing Wang, Yudong Ma, Tong Bu, Zile Gong, Xueyan Liu, Changcai Bai, Xiaolou Miao, Xiaofei Shang   +11 more
wiley   +1 more source

Targeting Tex10 Overcomes Oxaliplatin Resistance by Competitively Disrupting the Non‐Canonical BAF Complex in Colorectal Cancer

Advanced Science, EarlyView.
This study reveals that Tex10 drives oxaliplatin resistance in colorectal cancer by competitively binding BRD9 to disrupt the ncBAF complex, thereby suppressing AMBRA1 transcription and ULK1‐mediated autophagy. Gemcitabine is identified as a direct Tex10 inhibitor that restores autophagy and overcomes resistance.
Ping Xu, Jie Huang, Xiaojin Gao, Lin Deng, Yanheng Deng, Denglu Wang, Chunlei Yu, Yunxiang Zhang, Jingdong Li, Xiaocong Xiang   +9 more
wiley   +1 more source

Rhoifolin Alleviates Ulcerative Colitis by Targeting NMNAT1 and Activating SIRT1‐FOXO1 Signaling to Enhance ILC3s Effector Function

Advanced Science, EarlyView.
Rhoifolin directly targets NMNAT1, thereby activating nicotinamide salvage pathway and promoting intracellular NAD+ biosynthesis. Elevated NAD+ levels enhance SIRT1 activity, leading to FOXO1 deacetylation and nuclear translocation. Nuclear FOXO1 subsequently binds to the IL‐22 promoter, upregulating IL‐22 transcription and potentiating ILC3 effector ...
Hongqiong Yang, Yishu Zhang, Sijia Feng, Xiaoqing Ma, Jiayi Feng, Junwei Wang, Jialin Gao, An Pan, Dapeng Wu, Kang Ding, Caijuan Zheng, Qi Lv, Lihong Hu   +12 more
wiley   +1 more source

METTL7A Downregulation Drives SLC1A5‐Mediated Glutamine Competition to Promote Tumor Proliferation and Suppress CD8+ T Cell Immunity in Gastric Cancer

Advanced Science, EarlyView.
GC cells enhance glutamine accumulation by upregulating SLC1A5 expression. This upregulation not only boosts GC cell proliferation, but also outcompetes CD8+ T cells for glutamine and suppresses their antitumor immunity. Mechanistically, METTL7A deficiency in GC induces SLC1A5 overexpression via an m6A‐dependent pathway and N‐glycosylation ...
Mingjun Sun, Shuwei Dang, Dazhi Zhou, Lixian Ding, Xun Sun, Wei Suo, Jirui Niu, Qingzhu Yang, Zhicheng Zhang, Yanyan Sun, Jinxing Li, Zhongsheng Chen, Tao Ban, Yingji Wang, Tianzhu Li, Ming Liu, Guodong Li   +16 more
wiley   +1 more source