Reactive oxygen species (ROS) promote genomic instability and fuel oncogenic signaling in cancer, but antioxidant therapies have so far failed to improve, or worsen, cancer outcomes. Emerging data sug...

TRI-611 induces the degradation of ALK fusion proteins via a previously undescribed CRBN recruitment motif, and its preclinical anti-tumour activity highlights TRI-611 as a potential new way of treati...

Senescent cell states arise across brain-barrier cell types during development but diverge in duration and function. Endothelial cells and macrophages enter a transient, inflammatory state, whereas ch...

Signal Transduction and Targeted Therapy - Partial downregulation of platelet glycoprotein VI by low affinity antibodies confers sustained and safe antithrombotic protection

Just as Antelope Canyon transforms familiar rock into an unexpected hidden landscape, the topological inversion of Src reveals an unforeseen extracellular facet of kinase signaling in cancer. Antelop...

Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, w...

Just as Antelope Canyon transforms familiar rock into an unexpected hidden landscape, the topological inversion of Src reveals an unforeseen extracellular facet of kinase signaling in cancer. Antelop...

The ubiquitin-specific protease (USP) USP9X is a human deubiquitinase (DUB) with a large number of described targets and cellular roles. In cancer, USP9X is found as an oncogene or as a tumour suppres...

YAP is a key oncogenic driver that has long been considered undruggable. Here, the authors present the development of a nanobody-based bioPROTAC that efficiently degrades endogenous YAP, demonstrating...

Fluorescent proteins fused with nuclear (NLS) or nucleolar (NoLS) localization signals are commonly used for live assessment of protein accumulation in the nucleus and nucleolus. We present a standar...

Loss of the cargo receptor Erv14 in Saccharomyces cerevisiae results in sensitivity to calcium, zinc, neutral extracellular pH, and elevated temperature. Furthermore, cells deleted in the ERV14 exhib...

Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, ...

McKellar et al. have discovered that some satellite viruses act as the ultimate hitchhikers. They physically become a virus inside a virus, hiding within helper virus particles by hitching a ride as a...

This study describes the cell-type-specific lysosomal proteome across the major brain cell types and identifies SLC45A1 as a neuron-specific lysosomal sugar exporter linked to lysosomal storage diseas...

Oxytocin (OT) plays an important role in regulating social behavior, and dysregulation of the oxytocinergic system leads to social impairments, such as autism spectrum disorder. Central OT release is...

Mitochondria that are transported from satellite glial cells in dorsal root ganglia to peripheral sensory neurons through tunneling nanotube-like structures provide protection against peripheral neuro...

Overexpression of the proto-oncogene Src is common to a wide variety of cancers. In this work, we found that Src is noncanonically translocated and inverted onto the cell surface in cancer, both in vi...

Ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic dissemination through epigenetic activation of the integrate...

DNA-protein cross-links (DPCs) are highly toxic DNA lesions that block replication and transcription, but their impact on organismal physiology is unclear. We identified a role for the metalloprotease...

Once viewed solely as degradative compartments, lysosomes shape cell fate through signaling, metabolism, and communication. In glioblastoma, their rew…

The ALPK1 agonist UDSP-Hep stimulates tumour-cell antigen presentation, macrophage–DC cross-priming and differentiation of protective memory T cells.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several t...

How tumor cells overcome anti-tumor immune responses and drive cancer recurrence is not well understood. Yu et al. demonstrate how therapy-resistant breast cancer cells synthesize and secrete arachido...

Meningeal blood vessel blockage enhances anti-tumor immunity against GBM in preclinical models by expanding dural resident border-associated macrophages, which are equipped with an elevated antigen-pr...

Platelet integrin αIIbβ3 is essential for hemostasis, thrombosis, and inflammation. We found that ligation of αIIbβ3 by von Willebrand factor or fibrin under flow triggered its accumulation in plasma ...

Identifying the cell of origin that harbors an initial driver mutation is key to understanding tumor evolution and for the development of new treatments. For isocitrate dehydrogenase (IDH)–mutant glio...

Live-cell imaging of mRNA encoding secretome proteins and translated nascent peptide markers show that secretome translation occurs at endoplasmic reticulum junctions near lysosomes, requires lun...

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Mechanical forces influence cellular decisions to grow, die, or differentiate, through largely mysterious mechanisms. Separately, changes in resting m…

This review mainly discusses the role of ferroptosis in cervical cancer from four aspects: underlying mechanisms, stage-specific sensitivity, ferroptosis-related targets and biomarkers, and clinical ...

Chagas disease, caused by Trypanosoma cruzi, remains a major treatment challenge due to variations in host immunity and parasite strains. We found that small extracellular vesicles (EVs) from infecte...

While proteins bearing N-terminal signal or leader sequences are secreted via the ER-Golgi-plasma membrane axis of the conventional secretion pathway, many cytosolic proteins lacking signaling sequen...

Mechanisms of sEV uptake:① Membrane fusion.② Endocytosis.③ Receptor-ligand interaction.

Creative experiences such as dance, music, drawing, and strategy video games might preserve brain health. The authors show that regular practice or short training in these activities is linked to brai...

Lysosomal vacuolation is commonly found in many pathophysiological conditions, but its molecular mechanisms and functions remain largely unknown. Here, we show that the endoplasmic reticulum (ER)–anch...

Protein-protein interactions (PPIs) are essential for biological function. Coevolutionary analysis and deep-learning (DL)–based protein structure prediction have enabled comprehensive PPI identificati...

Cytosolic nucleic acid–sensing pathways are potential targets for cancer immunotherapy. Although stimulator of interferon genes (STING) agonists have shown substantial antitumor effects in animal mode...