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Moro et al. discover an Argonaute 2 (Ago2)-dependent miRNA network that, in response to substrate stiffness, regulates genes involved in tissue mechanics, and show that Ago2 restrains stiffness and contributes to regeneration in the zebrafish fin fold.
Kraft et al. show that chromosomal inversions that relocate a limb enhancer can establish asymmetric stripes of the enhancer with downstream genes, resulting in ectopic gene expression and limb phenotypes.
Cell metabolism ensures that cell dynamics and continued renewal are supported by a constant flow of matter that consumes energy. A new study shows that cell metabolism is sensitive to mechanical cues, revealing that the level of cell contraction modulates the production and storage of lipids, which could serve as fuel for energy production.
Romani et al. identify a response to reduced actomyosin contractility involving inhibition of Lipin-1, accumulation of SREBP transcription factors at the Golgi apparatus and activation of SREBP transcription driving increased lipid synthesis.
Science thrives on the free exchange of ideas and collaboration between diverse groups, with researcher mobility greatly accelerating progress. With isolationist rhetoric increasingly dominating the political discourse in many countries, it is important to recognize the value of migration in science.
Patients with diabetes could benefit from cell-based insulin therapy, but the supply of human islet tissue is limited. A study now reports an approach in which human-pluripotent-stem-cell-derived islet β-cells are purified and re-aggregated to generate cells that more closely resemble mature human β-cells.
Nair et al. report the generation of human ESC-derived mature and functional β cells in vitro with a culture system including a step to induce clustering of immature β-like cells.
AKT, also known as protein kinase B, is one of the most frequently dysregulated serine/threonine kinases in cancer, and its hyperactivity drives tumorigenesis and chemotherapy resistance. Two studies now find that AKT methylation by the methyltransferase SETDB1 is an early step in its oncogenic activation.
Guo et al. identify SETDB1 and KDM4B as the methyltransferase and demethylase, respectively, for AKT. AKT methylation promotes its kinase activity and the subsequent tumorigenesis.
Wang et al. show that Akt methylation by SETDB1 is
recognized by demethylase JMJD2A, which then recruits E3 ligases to
induce K63-linked Akt ubiquitination, leading to Akt activation and
tumorigenesis.
Stressed eukaryotic cells store mRNAs in protein-rich condensates called stress granules. Using single-molecule tracking techniques to examine how mRNAs enter stress granules, a new study shows that mRNAs make transient contacts with the granule surface before stable association, and become largely immobile after entry.
It is commonly accepted that disseminated tumour cells survive cytotoxic chemotherapy because they are not proliferating. A new study now finds that, in contrast to this long-standing concept, both dormant and proliferative cancer cells can be protected from chemotherapy when they reside at the perivascular niche.
Zhang et al. show that ALK phosphorylates SMAD4 at Tyr 95 to block its binding to DNA, representing a mutation-independent mechanism for blocking the tumour suppressor function of TGF-β in ALK-positive cancers.
Carlson et al. show that DTCs within the PVN are protected from chemotherapy; targeting interactions between DTCs and the PVN enhances chemosensitivity and prevents bone metastasis.
Performing a small-molecule screen, Liu et al. identify IRAK as a regulator of PIDDosome activity and tumour radioresistance, and demonstrate a synergistic effect of targeting IRAK1 and PIN1 in response to ionizing radiation.
By using multicolour single-molecule live imaging, Moon et al. show that the dynamics of the interaction between mRNAs and ribonucleoprotein granules are affected by translational status, mRNA length and granule size.
Li et al. show that the epithelial–mesenchymal-transition transcription factor Snail induces claudin-11 expression and suppresses RhoA activity, thereby promoting collective migration and tumour progression in head and neck cancer.
This year marks the twentieth anniversary of the launch of Nature Cell Biology. We take this opportunity to reflect on the progress in cell biological research and the evolution of our journal, and to celebrate the start of our third decade with a special Focus on 20 years of cell biology.