390 papers
This study demonstrates that while the human oncoprotein EWS::FLI1 can function as a pioneer factor to convert silent GGAASat sequences into active enhancers in *Saccharomyces cerevisiae* despite the absence of key animal-specific cofactors, its ability to drive extensive transcriptome reprogramming relies on evolutionarily recent animal-specific pathways.
This study reveals that Menin acts as a context-dependent regulator of enhancer-promoter architecture, where its inhibition causes broad transcriptional dysregulation and disrupts enhancer connectivity specifically in MLL-rearranged leukemia but not in NPM1-mutant leukemia, thereby identifying enhancer-promoter interactions as a selective therapeutic vulnerability in the former.
This study demonstrates that the Notch1/Delta-like-4 signaling axis acts as a central oncogenic driver in oral squamous cell carcinoma, characterized by specific expression patterns distinct from Jagged1 that emerge early in tumor development and promote cancer progression.
This study identifies EZH1 upregulation as a resistance mechanism to PI3K inhibition in acute myeloid leukemia leukemic stem cells and demonstrates that combining a PI3K inhibitor with an EZH1/2 dual inhibitor overcomes this resistance to effectively target the disease in preclinical models.
This study utilizes single-cell and multi-omics analyses to reveal that while BRCA1 and BRCA2 somatic mutations in lung adenocarcinoma drive distinct transcriptional programs and immune microenvironment alterations—such as differential T cell activation and tissue-resident memory T cell expansion—they collectively predict improved responses to immune checkpoint blockade despite being associated with genomic instability and poor prognosis.
This study reveals that combining CDK9 inhibitors with neuropsychiatric drugs, such as SSRIs, synergistically suppresses diffuse midline glioma growth by modulating H3 dopaminylation and inhibiting pro-survival CaMKII signaling, thereby overcoming transcriptional resistance mechanisms.
This study demonstrates that the cooperative loss of KIF1Bβ and Nf1 drives sympathoadrenal lineage plasticity, enabling chromaffin-to-neuroblast reprogramming through developmental intermediates to generate heterogeneous paraganglioma, neuroblastoma, and composite tumors, a mechanism confirmed by both mouse models and human spatial transcriptomics.
This study demonstrates that intratumoural administration of the oncolytic HSV-1 RP1 induces regression of both injected and distant melanomas by reprogramming systemic CD8+ T cell immunity through the generation of self-renewing, antigen-engaged "viral-induced precursors," whose associated gene signature correlates with improved clinical responses to immunotherapy.
This study integrates genomic, transcriptomic, and clinical data from 348 pancreatic cancer patients to demonstrate that non-glandular morphological subtypes (cribriform, solid, and squamous) represent biologically distinct states enriched in metastatic disease, characterized by specific transcriptional programs and KRAS-driven genomic alterations.
This study reveals that antibodies against a specific enterovirus epitope (CE1) protect against hepatocellular carcinoma by cross-reacting with the tumor-associated protein ASPH via molecular mimicry, thereby triggering NK cell-mediated tumor destruction.
This study demonstrates that multi-region biopsies and derived neurosphere cultures from glioblastoma patients exhibit significant spatial heterogeneity in phenotypes, proliferation, and drug responses, highlighting the necessity of using multi-region models to accurately capture intratumor diversity for effective therapeutic testing.
This study demonstrates that extracellular signaling induces phosphorylation of Menin at Ser487, which restricts its nuclear accumulation and relieves transcriptional repression of gastrin, thereby contributing to neuroendocrine tumorigenesis.
This study demonstrates that KRAS inhibitors effectively suppress tumor growth in appendiceal adenocarcinoma by inhibiting RAS/ERK signaling and remodeling the tumor microenvironment to enhance innate immune responses, although adaptive activation of EMT and TGF-β pathways may drive resistance, supporting the continued clinical development of these agents, potentially in combination with resistance-targeting strategies.
This study introduces vmwhere, a computational framework for analyzing tetrameric microsatellites from long-read sequencing data, and demonstrates that in Ewing sarcoma, longer GGAA repeat lengths drive increased EWS-FLI1 binding and chromatin accessibility, thereby linking repeat architecture to regulatory function.
Through CRISPR screening and epigenomic analysis, this study identifies POU2F1 as a critical, context-specific transcriptional activator of DLL3 and neuroendocrine identity in small cell lung cancer, operating via a tandem cis-regulatory code with ASCL1.
This study reveals that the HPV E7 oncoprotein drives LASP1 transcription in HPV-positive cervical cancer cells by degrading Rb to activate E2F1, which directly binds to and promotes the LASP1 promoter, thereby establishing an additional mechanism alongside miR-203 downregulation that underscores LASP1's critical role in cancer progression.
This study demonstrates that patient-derived lung cancer organoids successfully replicate the unique histological features, including keratin pearl structures and specific tumor markers, of their parent keratinizing squamous cell carcinomas, establishing them as high-fidelity 3D models for advancing preclinical drug testing and understanding tumor biology.
This study demonstrates that CA19-9 drives pancreatic cancer liver metastasis by mediating E-selectin-dependent tumor cell extravasation and promoting AKT-associated outgrowth, thereby establishing it as a functional driver and potential therapeutic target.
This study demonstrates that the transcription factor FOXA1 maintains epithelial cell polarity and suppresses lysosome biogenesis in non-small cell lung adenocarcinoma by competing with TFE3 at enhancers, thereby revealing a novel FOXA1-TFE3-lysosome axis as a potential therapeutic target to inhibit tumor plasticity and progression.
This study demonstrates that in a *Drosophila* model of prostate cancer, the loss of canonical sex steroid signaling promotes tumor progression and escape by inducing a new tumor cell population through altered basal extrusion mechanisms, challenging the assumption that such signaling deprivation solely inhibits cancer growth.