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Wu et al. report that a stiff extracellular matrix stimulates the release of exosomes from cancer cells under the control of Akt and Rab8. These exosomes in turn promote tumour growth.
Zanin, Viaris de Lesegno et al. identify what controls the endosomal activation of the IFNAR receptor by IFN-α and establish a central role for endosomal sorting via STAM and Hrs in the differential regulation of JAK–STAT signalling by IFN-α and IFN-β.
Liu, Nie et al. identify disulfidptosis as a form of cell death resulting from aberrant accumulation of disulfide bonds in actin cytoskeleton proteins that is induced following glucose starvation and dependent on SLC7A11-mediated cystine uptake.
Harasimov et al. show that, in human and porcine oocytes, actin cables and microtubule loops move chromosomes into a cluster before spindle assembly to ensure fast and complete chromosome capture in meiosis.
Hu et al. report that patient-derived YAP fusion proteins undergo liquid–liquid phase separation in the nucleus to drive ependymoma tumourigenesis, altering transcription through transcription factor recruitment and alteration of genomic methylation.
Huebner et al. develop a 2D culture system to study gastric isthmus stem cells and identify a role for Sox2 in specifying enterochromaffin cells in the stomach.
Martino, Sunkara et al. report that endothelin produced by hair follicle progenitors binds to endothelin receptors on dermal sheath cells to trigger their contraction and hair follicle regression.
Wong et al. report that expanding human embryonic stem cell-derived endodermal progenitors serve as a ventral foregut model, through which they identify a link between progenitor expansion and tissue-specific changes in the enhancer landscape.
Adriaenssens et al. provide evidence suggesting that cytosolic small heat shock proteins localize to the mitochondrial intermembrane space, where they operate as molecular chaperones.
Independent but complementary studies from Vakoc and Stegmaier identify and characterize a role for ETV6 in counteracting the transcriptional activity of EWS–FLI during Ewing sarcoma development, which may be targeted for therapeutic benefits.
Deshwal et al. show that the protease PARL regulates coenzyme Q (CoQ) via the lipid transfer protein STARD7. Mitochondrial STARD7 ensures CoQ synthesis; cytosolic STARD7 preserves CoQ transport to the membrane, protecting cells against ferroptosis.
Independent but complementary studies from Vakoc and Stegmaier identify and characterize a role for ETV6 in counteracting the transcriptional activity of EWS-FLI1 during Ewing sarcoma development, which may be targeted for therapeutic benefits.
Mitchell et al. identify reduced osteoprogenitors and increased mesenchymal stromal cells in old bone marrow niche, which creates an IL1-mediated inflammatory milieu that skews myeloid differentiation and impairs haematopoietic regeneration.
Liu et al. demonstrate that CK2 phosphorylates CLOCK to promote its nuclear exportation and cytosolic accumulation, thereby acetylating and stabilizing PRPS1/2 and enhancing de novo nucleotide synthesis to facilitate liver tumour growth.
Wu et al. identify a mechanistic role for LPAR4 in promoting a fibronectin-rich extracellular matrix via AKT, CREB and integrins, thereby generating a niche that facilitates initiation of pancreatic cancer.
Using somatic genome editing and Tuba-seq, Tang et al. uncover a previously uncharacterized role for HRAS and NRAS in impairing KRAS–KRAS interaction to suppress lung tumour growth.
With whole-genome screens using a bivalent MHC class I gene expression readout, Sparbier et al. identify opposing roles for Menin and KMT2A/B in modulating activating H3K4me3 versus repressive H3K27me3 at bivalent promoters to regulate gene activation.
Polycomb repressive complexes 1 and 2 both regulate maintenance of X inactivation in extra-embryonic lineages of post-implantation embryos by affecting overlapping yet different genes, thus implying potentially independent roles for the two complexes.
Jung-Garcia et al. dissect the contributions of isoforms of the inner nuclear membrane protein LAP1 to nuclear envelope blebbing, constrained migration and invasion in melanoma cells.