Volume 21 Issue 2, February 2019

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.

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.

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.

Moreno-Layseca et al. discuss how integrins, key receptors that mediate cell adhesion to the extracellular matrix, are endocytosed and recycled to the cell surface to modulate cell and tissue behaviour.

In this Review, Lawrence and Zoncu discuss the central role of the lysosome in cellular metabolism, including in macromolecular catabolism and nutrient recycling, and organelle crosstalk. They highlight the emerging function of the lysosome as a centre for nutrient sensing and metabolic signal transduction.

Perez and Lehner summarize recent discoveries regarding epigenetic inheritance across generations and review the molecular mechanisms underlying non-DNA sequence-based transmissions.

Valencia and Kadoch review diverse functions of DNA and histone modifying proteins, and chromatin remodelling complexes in cancer, and discuss how these may be favourably leveraged for therapeutic development.

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.

Studying blastoderm spreading in zebrafish, Petridou et al. discover that this process is facilitated by tissue fluidization, mediated by a local loss of cell–cell adhesion during mitotic rounding and spatially restricted by Wnt.

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.

Keklikoglou et al. report that cytotoxic drugs induce tumour-derived extracellular vesicles that facilitate monocyte expansion through annexin A6 and thus lung metastasis in breast cancer.

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.

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.

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.

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.

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.

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.

Giulitti et al. deliver modified mRNAs encoding OCT3/4, SOX2, KLF4 and cMYC as well as NANOG in microfluidics to directly convert human fibroblasts into naive induced pluripotent stem cells; the confined environment leads to enhanced efficiency and homogeneity compared to traditional methods.

Harada et al. develop a chromatin integration labelling (ChIL) method to map distributions of histone modifications and DNA-binding factors at low-input or even single-cell levels.