Results 201 to 210 of about 628,495 (277)

Dual Aptamers‐Based SETDB1 PROTACs as Effective Anti‐Tumor Strategies for Breast Cancer

open access: yesAdvanced Science, EarlyView.
This study establishes dual‐aptamer PROTACs targeting SETDB1 using a SETDB1‐specific aptamer conjugated to AS1411. The designed PROTACs penetrate cells, recruit MDM2 to degrade SETDB1, and inhibit cancer cell proliferation and migration. Remarkably, they also overcome tamoxifen resistance and enhance CD8+ T cell cytotoxicity, suppressing tumor growth ...
Yanxuan Guo   +6 more
wiley   +1 more source

Pancancer Fine‐Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma

open access: yesAdvanced Science, EarlyView.
This study identifies mutation‐intolerant genes (MIGs), which are mutationally constrained in tumors despite normal‐tissue variability. Using miDriver, the authors pinpoint MIGs essential for tumor‐intrinsic fitness and immune evasion. Focusing on CHEK1, they show it drives tumor fitness and sculpts an immunosuppressive niche via the MIF–CD74 axis ...
Tao Wang   +16 more
wiley   +1 more source

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

open access: yesAdvanced 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   +10 more
wiley   +1 more source

The Age‐Dependent Resident Myonuclear Multi‐Omic Response to an Acute Skeletal Muscle Hypertrophic Stimulus in Mice

open access: yesAdvanced Science, EarlyView.
Resident myonuclei are the molecular “control centers” for large multinuclear muscle fibers. It is presumed that, with aging, these control centers become compromised and contribute to delayed or blunted muscle adaptive potential. This study is a detailed roadmap that exposes how young versus aged myonuclei respond to a hypertrophic loading stimulus ...
Pieter J. Koopmans   +8 more
wiley   +1 more source

m5C‐Modified tRF3b‐CysGCA‐23 Suppresses Bladder Cancer Malignancy by Repressing H3K18 Lactylation via Stabilizing RBM4

open access: yesAdvanced Science, EarlyView.
In this study, we identified an NSUN6‐dependent m5C‐modified tsRNA, m5C‐tRF3b CysGCA‐23 (mtRC), that is downregulated in BC and inversely correlated with disease progression. Mechanistically, mtRC suppresses BC malignancy by stabilizing RBM4, attenuating glycolysis, and thereby limiting H3K18 lactylation–mediated activation of IL1RAP and VASH2 ...
Xiaoling Ying   +16 more
wiley   +1 more source

POU2F1 Promotes Chemoresistance in Colorectal Cancer Cells via Attenuates the MDR2 Degradation Mediated by PPP1R11 Lactylation

open access: yesAdvanced Science, EarlyView.
Schematic diagram of our study showing that highly expressed POU2F1 in colorectal cancer (CRC) can directly accelerate the cytosolic lactate export to decrease PPP1R11 lactylation at K59, thereby attenuating the E3 ligase enzyme activity and protein stability of PPP1R11, which inhibits the ubiquitination of MDR2 at K413 and K538 but increases the ...
Longzheng Xia   +8 more
wiley   +1 more source

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