Volume 20 Issue 8, August 2018

Metastatic colonization of distant organs is the prime cause of mortality from cancer, and is governed by a series of steps that include survival and growth in the perivascular niche. A study now shows that L1CAM is necessary for tight physical interactions in this niche, involving a YAP–MRTF–β1-integrin mechanotransduction pathway.

A previously unidentified protein complex termed Shieldin acts with the nucleosome-binding protein 53BP1 to limit end resection at DNA double-strand breaks, impacting myriad biological outcomes, from immunology to cancer therapy, and highlighting the importance of chromatin responses to DNA damage in vertebrates.

Enteroendocrine (EE) cells secrete diverse peptide hormones, regulating food intake, digestion and metabolism. A study now challenges the traditional view that each hormone is the dominant product of a distinct EE cell type, showing that in response to local cues the same cell produces different hormones in different tissue compartments.

Skeletal muscle denervation leads to myofibre atrophy with fibrosis and fatty infiltration of muscle-resident fibroadipogenic progenitors (FAPs). A study shows that on denervation, FAPs activate pathogenic STAT3–IL-6 signalling. Inhibition of this pathway prevents atrophy and points to potential therapeutic targets.

Celia-Terrassa and Kang discuss specialized functions of distinct metastatic niches, and how the emerging knowledge can be leveraged for improved therapeutic opportunities.

Shahbazi et al. review our current understanding of the post-implantation mammalian embryo and how innovative technologies have helped to shape it.

Stefano Piccolo and co-authors review recent insights into how YAP and TAZ transcription factors respond to the tissue environment, and how they mediate altered cell behaviour. Feedback mechanisms and crosstalk with other pathways are discussed, as are outstanding questions in the field.

Using a heterokaryon system, Mai et al. demonstrate that NKX3-1 is downstream of IL-6–STAT3, regulates endogenous OCT4 expression during human iPSC reprogramming, and can also substitute for exogenous OCT4 in the reprogramming cocktail.

Beumer et al. show that intestinal enteroendocrine cells adjust their hormonal profile during migration from the crypt to the villus, depending on region-specific BMP signalling.

Madaro et al. show that denervation induces accumulation of IL-6–STAT3-activated fibro-adipogenic progenitors without inflammation or muscle regeneration, leading to muscle atrophy and fibrosis.

Using electron and three-dimensional structured illumination microscopy methods, Jana et al. characterize the ciliary base in four different cilia types in Drosophila, discovering structural and protein component differences that may be linked to the diversified functions of cilia.

Urra et al. discover that IRE1α, an ER stress mediator, interacts with filamin A and controls actin dynamics and cell migration in mouse, Drosophila and zebrafish models in a manner independent of its canonical function.

Through CRISPR–Cas9 screen, Dev et al. identified that SHLD1/2 inhibition contributes to PARP-inhibitor resistance. Mechanistically, SHLDs promote non-homologous end-joining and antagonize homologous recombination.

Massagué and colleagues show that disseminated cancer cells use L1CAM to spread on capillaries and to achieve their outgrowth through activating YAP signalling.

Sozen et al. devise an approach to combine embryonic stem cells, trophoblast stem cells and extra-embryonic endoderm stem cells into self-assembling embryo-like structures, which recapitulate key hallmarks of gastrulation in vitro.