Cell Reports

Hypoxia restores the acidosis-induced inhibition of cancer cell dissemination Lee et al. reveal that short-term acidosis suppresses cancer cell aggressiveness across cell types. Hypoxia overrides acidosis-mediated inhibition of motility by restoring NHE1/ILK function and maintaining bioenergetic balance through compensatory glycolysis. Adaptation to chronic acidosis is cell-specific and depends on a cell’s ability to restrain ROS via fatty acid oxidation.

Hypoxia restores the acidosis-induced inhibition of cancer cell dissemination

High-throughput engineered tumor organoids reveal ROCK signaling as an immunotherapeutic target in triple-negative breast cancer Ma et al. developed a TIL-competent triple-negative breast cancer (TNBC) organoid model recapitulating the immune microenvironment. They identified pentanoic acid as a ROCK activator that preserves tumor-infiltrating lymphocytes and enhances the anti-PD-1 immunotherapy efficacy, providing potential precision medicine strategies for aggressive basal-like immune-suppressed (BLIS) subtypes.

High-throughput engineered tumor organoids reveal ROCK signaling as an immunotherapeutic target in triple-negative breast cancer

Circadian rhythm heterogeneity modulates drug response variations in neuroblastoma models Ector et al. uncover circadian heterogeneity across neuroblastoma cell models and link rhythmic strength to drug sensitivity. Their findings suggest that circadian competence may influence treatment outcomes, pointing to chronotherapy as a potential avenue for improving pediatric cancer care.

Circadian rhythm heterogeneity modulates drug response variations in neuroblastoma models

A CRISPR-based mitochondrial gene therapy tool derived by engineering guide RNAs Wang et al. systematically analyzed mitochondria-localized lncRNAs to reveal that RBP-motif recognition drives RNA mitochondrial translocation, leading to the engineering of an RNA mitochondrial targeting sequence (RMTS). Fusing RMTS with sgRNA promotes sgRNA mitochondrial entry, establishing a CRISPR-based mitochondrial DNA editing system that ameliorates heteroplasmic mtDNA mutation diseases.

A CRISPR-based mitochondrial gene therapy tool derived by engineering guide RNAs

Triglycerides induce endoplasmic reticulum lipid bilayer stress to activate PERK and enhance antifungal immunity Fungal infections can induce ER stress, but whether ER stress affects antifungal immune signaling remains unclear. Wu et al. reveal that upon fungal stimulation, the PERK branch of the unfolded protein response pathway is activated by triglyceride synthesis and then mediates autophagic degradation of SHP-1 to amplify SYK-associated antifungal immunity.

Triglycerides induce endoplasmic reticulum lipid bilayer stress to activate PERK and enhance antifungal immunity

RAB3GAP2 is a regulator of skeletal muscle endothelial cell proliferation and associated with capillary-to-fiber ratio Ström et al. identify the rs115660502 variant in RAB3GAP2 associated with increased skeletal muscle capillary-to-fiber ratio and enriched in endurance athletes. This variant reduces RAB3GAP2 expression, enhancing endothelial proliferation, tube formation, and TNC secretion, thereby promoting exercise-like angiogenesis and microvascular remodeling in skeletal muscle.

RAB3GAP2 is a regulator of skeletal muscle endothelial cell proliferation and associated with capillary-to-fiber ratio

A bicistronic viral genome uses a compact type IV IRES near its 3′ end to express a transmembrane protein Sherlock et al. examine an IRES RNA that initiates translation of a small downstream coding region within a viral genome. The structure, function, and mechanism of this IRES are interrogated experimentally. Differential translation efficiencies between two IRESs within one viral genome exemplify RNA-structure-based tuning of gene expression.

A bicistronic viral genome uses a compact type IV IRES near its 3′ end to express a transmembrane protein

Nuclear PD-L1 regulates YAP-driven transcription via the PGE2-EP4-YAP-importin α3 axis in solid tumors Satapathy et al. demonstrate that prostaglandin E2 promotes YAP-dependent nuclear translocation of PD-L1 via importin-α3. In the nucleus, PD-L1 cooperates with YAP-TEAD to enhance transcriptional activity, revealing a noncanonical role for PD-L1 in regulating oncogenic gene expression beyond immune evasion.

Nuclear PD-L1 regulates YAP-driven transcription via the PGE2-EP4-YAP-importin α3 axis in solid tumors

For a chance to present your research as a poster or short talk @CellSymposia #CSMito2026 in Glasgow, Scotland, June 21–23, 2026, submit an abstract of your work before March 9
Submit here: http://dlvr.it/TRC29Y

Cellular Mg2+ decrease causes a distinctive NF-κB-dependent form of cell death Mg2+ is crucial for various cellular functions, but the effect of intracellular Mg2+ decrease remains obscure. Kawamura et al. show that the decrease triggers massive cell death by activating the NF-κB signal. Furthermore, cell death is distinct from the known types of regulated cell death, which are characterized by actin-driven protrusions.

Cellular Mg2+ decrease causes a distinctive NF-κB-dependent form of cell death

Tfam-mediated metabolic perturbation in RORγt+ lymphocytes impacts intestinal tissue homeostasis and promotes GATA3+RORγt+ innate lymphoid cells Sun et al. report an indispensable role for Th2 cells in small intestine lengthening driven by tuft cell type 2 immunity and a population of GATA3+RORγt+ ILCs promoted by Tfam deficiency, high-fat diet, and DSS-induced gut inflammation in mice. GATA3+RORγt+ ILCs exhibit transcriptional and metabolic profiles distinct from that of conventional ILC3s.

Tfam-mediated metabolic perturbation in RORγt+ lymphocytes impacts intestinal tissue homeostasis and promotes GATA3+RORγt+ innate lymphoid cells

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Excited to hear @nataliekrahmer.bsky.social discuss "Elucidating the cell architecture of metabolic liver disease" at Cell Press Symposia #CSMito2026 (June 21–23, 2026, Glasgow, Scotland)
Submit an abstract before March 9 to join her: http://dlvr.it/TRBjrq

MARK2 serves as a key regulator of host antiviral immunity through GEF-H1 phosphorylation Wang et al. identify MARK2 as a key regulator of innate antiviral immunity. The phosphorylation of GEF-H1 at Ser645 by MARK2 enhances TBK1 activation and induces IFN-β andIFN-stimulated genes. This establishes the MARK2-GEF-H1-TBK1 axis as a fundamental component of host antiviral defense.

MARK2 serves as a key regulator of host antiviral immunity through GEF-H1 phosphorylation

Revealing an unconventional JAK1/2-STAT3 branch in macrophage IFN-γ signaling Botman et al. reveal that IFN-γ can rapidly activate STAT3 in macrophages, forming STAT1-STAT3 heterodimers that fine-tune gene expression. This discovery uncovers a new layer of complexity in cytokine signaling and macrophage activation, broadening our understanding of immune regulation.

Revealing an unconventional JAK1/2-STAT3 branch in macrophage IFN-γ signaling

Unveiling hidden variables in stressed bacteria Noise in bacterial stress responses is often dismissed as mere randomness. While true stochasticity exists, much variation reflects hidden variables—cell state, history, and microenvironment—that are only now becoming measurable. Choudhary and Vincent review emerging tools that disentangle chance from determinism, moving microbiology toward more mechanistic and predictive frameworks.

Unveiling hidden variables in stressed bacteria

SNAP25 undergoes phase separation to facilitate the assembly of the synaptic vesicle fusion machinery Zhu et al. find that SNAP25, a key SNARE protein involved in synaptic vesicle fusion, undergoes phase separation, which is regulated by palmitoylation modification and interaction with syntaxin-1. The SNAP25 condensates recruit syntaxin-1 and VAMP2 to form coacervates, facilitating vesicle docking and the assembly of the SNARE complex.

SNAP25 undergoes phase separation to facilitate the assembly of the synaptic vesicle fusion machinery

Ploidy and neuron size impact nervous system development and function in Xenopus Liu et al. use triploid Xenopus as a model to characterize effects of neuron size on vertebrate nervous system development and function. They report association between neuron size, cell proliferation, brain activity, and tadpole swimming behavior.

Ploidy and neuron size impact nervous system development and function in Xenopus

Histamine H3 receptors in the paraventricular thalamus link sleep loss to fat overconsumption Xinyue Zhao et al. show that sleep restriction causes histamine accumulation in the paraventricular thalamus (PVT), which downregulates H3 receptors (H3Rs), reduces the excitability of PVT fat-responsive neurons, and ultimately induces a selective preference for a high-fat diet. This reveals PVT-H3R signaling as a key mechanism linking sleep loss to aberrant feeding.

Histamine H3 receptors in the paraventricular thalamus link sleep loss to fat overconsumption

Porcine IRF2 suppresses the cGAS-STING-mediated antiviral IFN signaling by competing IRF3 for binding to the IFN promoter Sen Jiang et al. identify porcine IRF2 as a potent inhibitor of innate immune cGAS-STING-IRF3-IFN antiviral signaling pathway via systemic screenings, and they further dissected the mechanism of action by porcine IRF2 for negative regulation. This research unveiled a distinct function of IRF2 and provides justification for intervention of porcine viral diseases.

Porcine IRF2 suppresses the cGAS-STING-mediated antiviral IFN signaling by competing IRF3 for binding to the IFN promoter

Ptprf is the conserved receptor for Asprosin’s glucogenic effects in vertebrates Liu, Z. et al. identify protein tyrosine phosphatase receptor F (Ptprf) as the receptor for the glucogenic hormone Asprosin. Genetic ablation and overexpression demonstrate the essential role of Ptprf in mediating Asprosin-induced hyperglycemia. These findings establish the conserved Asprosin-Ptprf axis as a promising therapeutic target for diabetes and obesity.

Ptprf is the conserved receptor for Asprosin’s glucogenic effects in vertebrates

Humanization and engineering of protective antibodies targeting severe fever with thrombocytopenia syndrome virus Gn protein Ren et al. humanize and structurally optimize a chimeric anti-SFTSV antibody, generating variants with markedly enhanced neutralization potency by strengthening binding to recombinant Gn and intact virions, providing full in vivo protection and establishing a generalizable framework for therapeutic antibody engineering.

Humanization and engineering of protective antibodies targeting severe fever with thrombocytopenia syndrome virus Gn protein

Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools Stunault et al. show that the ketogenic diet drives extensive transcriptional reprogramming of the hippocampus through histone post-translational modifications, leading to altered short-term plasticity and reduced synaptic integration at the circuit level.

Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools

Cell-type-independent infection dynamics of clinical Pseudomonas aeruginosa isolates in human airway epithelial models Colque et al. uncover how Pseudomonas aeruginosa persists in cystic fibrosis airways despite treatment. Their work shows that bacterial adaptation, not just antibiotic resistance, drives chronic infection, offering a new framework for understanding persistence and guiding better therapies.

Cell-type-independent infection dynamics of clinical Pseudomonas aeruginosa isolates in human airway epithelial models

SERPINA3 mediates liver cancer cells escape from chemotherapy-induced neutrophil extracellular trap killing Liver cancer frequently exhibits chemoresistance in clinical settings. Zhang et al. report that a member of the serine protease inhibitor family, SERPINA3, mediates this resistance primarily by inhibiting the protease cathepsin G (CTSG), which is released by chemotherapy-induced neutrophil extracellular traps (NETs). Targeting SERPINA3 sensitized liver cancer cells to chemotherapy.

SERPINA3 mediates liver cancer cells escape from chemotherapy-induced neutrophil extracellular trap killing

Full dopamine coding of basic economic subjective value: Utility and weighted probability The value of rewards is subjective, extending beyond physical properties. The brain should thus represent subjective reward values. Ferrari-Toniolo et al. record the activity of primate dopamine neurons during choices and use economic theory approaches to assess the coding of the two most fundamental subjective value components: utility and weighted probability.

Full dopamine coding of basic economic subjective value: Utility and weighted probability

ESM1 SUMOylation mediates bevacizumab resistance in ovarian cancer through ITGB1-FAK-driven angiogenesis Ran et al. discover a new mechanism of resistance to bevacizumab for ovarian cancer therapy. They identify a protein, ESM1, whose SUMOylation drives angiogenesis in bevacizumab-resistant ovarian cancer, pointing to a promising new therapeutic target.

ESM1 SUMOylation mediates bevacizumab resistance in ovarian cancer through ITGB1-FAK-driven angiogenesis

Submit your abstract here

We’re pleased to invite abstracts for presentation @CellSymposia #CSCellDeath26 in Hangzhou, China, October 22–24, 2026. Submit your abstract before June 19 and help shape the future of cell death research.

Submit here: http://dlvr.it/TR6r9Y

Distances and charges along the Orai1 nexus-TM3 interface control STIM1 binding and pore opening Calcium influx through CRAC channels requires STIM1 binding to Orai1. Using crosslinking and mutagenesis, Söllner et al. show that widening the nexus-TM3 interface near the STIM1 coupling site is crucial for channel opening, while hydrophobicity and charges support signal transmission to the pore. Nexus-TM3 dynamics are vital for Orai1 function.

Distances and charges along the Orai1 nexus-TM3 interface control STIM1 binding and pore opening

GATA-3 localization shapes lymphocyte function Saikali et al. describe differential compartmentalization of GATA-3 in Th cell and ILC subsets. Changing it modifies functional characteristics of the cells. Importin-β mediates GATA-3’s nuclear import. The short half-life of nuclear GATA-3 necessitates continuous GATA-3 import to maintain Th2 cell function. GATA-3’s nuclear import is a critical rheostat of lymphocytes.

GATA-3 localization shapes lymphocyte function

Telomere-to-telomere assembly detects genomic diversity in Canadian strains of Borrelia burgdorferi Amin et al. present telomere-to-telomere assemblies of nine Borrelia burgdorferi strains from Canada, uncovering the diversity at chromosome ends and plasmid profiles. They identify an lp28-1a plasmid subtype and detect plasmid-chromosome recombination, offering insights into genomic plasticity and potential mechanisms of adaptation in Borrelia.

Telomere-to-telomere assembly detects genomic diversity in Canadian strains of Borrelia burgdorferi