News & Views

Fibroblasts become activated during wound repair and rapidly return to a ‘resting’ state, and are thus critical for normal tissue homeostasis and tumour development. A new study now reveals an important pro-tumorigenic role for the stress response in cancer-associated fibroblasts that may offer a new opportunity to limit tumour progression.

Although cardiac cell therapy has been intensely studied, the high expectations are still an unmet goal. A study now characterizes the translational potential and mode of action of human ventricular progenitors (HVPs) derived from embryonic stem cells, as a source for cardiac cell therapy.

Cytosolic DNA sensing by the cGAS–STING pathway is critical for sustaining an innate immune defense program. A new study shows that the cGAS–STING pathway signals by a non-canonical mechanism to control protein translation through the unfolded protein response sensor PERK, and thereby contributes to cellular senescence and organ fibrosis.

Phosphoinositide signalling regulates cellular processes and is hijacked by pathogens. Classically, phosphoinositides are produced by kinase- and phosphatase-catalysed reactions. A study now reveals an unprecedented, kinase- and ATP-free synthesis of PtdIns(3,4)P₂ via a phosphotransferase mechanism during bacterial infection.

Organic acidurias are inherited disorders that can severely affect mitochondria. A study in Caenorhabditis elegans suggests that binding of a toxic metabolite to a factor crucial for mitochondrial structure may contribute to disease mechanisms.

Overload of proteasomal clearance triggers formation of a large protein inclusion called the aggresome, which shares similarities with protein aggregates seen in neurodegenerative diseases such as Huntington’s. A new study uncovers how centrosome and centriolar satellite components facilitate stepwise assembly of aggresomes.

Biomolecular condensation has emerged as a fundamental mechanism for cellular organization, but less is known about the regulation of condensate subcellular location and size. A new study reports that membrane tethering of protein and RNA directly influences the assembly, size and material properties of ribonucleic condensates.

Epithelial to mesenchymal transitions (EMTs) drive cancer metastases. A series of single cell analyses now reveal this change in state is not binary and that two epigenetic complexes govern the convertibility of epithelial cells to mesenchymal states that are differentially conducive to metastasis.

Necrosomes formed by RIPK1–RIPK3 mediate necroptosis. Super-resolution microscopy identifies the architectural features of necrosomes and provides mechanistic insights into the signalling from RIPK1 to RIPK3 when RIPK1 is activated to mediate necroptosis, and from RIPK3 to RIPK1 when RIPK3 is inhibited to mediate apoptosis.

Tumour growth involves anomalies in cell cycle genes and emergent phenotypes, but the tumour proliferation rate (or mitotic index) is defined by just one marker, Ki-67. A study now integrates expression patterns of several markers to generate spatio-temporal maps of cell proliferation in cancer tissues.

Increased tRNA abundance and amino acid coupling generally promote increased oncogenesis. By contrast, a new study shows that in breast cancer, the leucyl-tRNA synthetase LARS suppresses transformation and tumour development by increasing tRNA-Leu^CAG translation of certain tumour suppressor mRNAs.

What does an actively transcribing genomic locus look like? A recent study has taken advantage of large and highly expressed mammalian genes and used microscopy to find out. The discovery sheds light on transcription and its effect on chromosome structure and the spatial organization of gene loci.

Haematopoiesis is a process relying on haematopoietic stem cells (HSCs) and their complex interactions with the microenvironment. A new study by Pinho et al. identifies the adhesion molecule VCAM1 as an immune checkpoint that protects haematopoietic stem and progenitor cells, as well as leukaemic cells, from monocytic phagocytosis.

The integrity of the mitochondrial genome (mitochondrial DNA) is crucial for energy synthesis in all complex life. A study now reveals a vicious cycle of mtDNA replication within dysfunctional mitochondria that preferentially propagates genomes carrying deleterious mutations.

Mitochondria are asymmetrically distributed to the daughter cells according to their age. A study now identifies metabolic features associated with mitochondrial age that regulate cell fate decisions.

Extracellular matrix (ECM) rigidity increases during tumour progression. In a recent study, Romani et al. delineated a connection between ECM stiffness and the redox response of disseminated tumour cells. Their results suggest that soft ECM promotes DRP1-mediated mitochondrial fission and an NRF2-dependent antioxidant response.

Synthesis of the neurotransmitter GABA (γ-aminobutyric acid) by glutamate decarboxylase (GAD) normally occurs in neurons. A study now shows that ectopic expression of GAD leads to GABA accumulation, enhanced tumour cell proliferation and immunosuppression, and blocking GABA signalling improves the anti-tumour efficacy of immunotherapy.

Epigenetic inheritance is the transfer of non-DNA information across generations. A new study identifies sperm-specific PEI granules as essential for paternal epigenetic inheritance. PEI granule partitioning to sperm requires palmitoylation and myosin VI activity, suggesting lipidation-dependent granule transport on vesicles.

Lipid metabolism is crucial for the execution of ferroptosis. A new study demonstrates that the function of the lipid metabolic enzyme ACSL4 is positively regulated by phosphorylation, leading to amplification of ferroptotic cell death. These results shed new light on the regulation of ferroptosis execution in cancer cells.

Nuclear pore complexes (NPCs) facilitate the fast, yet highly selective, nucleocytoplasmic transport of molecules. A recent study describes a multicolour imaging approach to chart the paths for cargo molecules through the human NPC with real-time 3D visualization of nucleocytoplasmic transport events with high spatial and temporal precision.