Volume 21 Issue 7, July 2019

Different subclones cooperate to support tumour heterogeneity and growth, but the effect on metastasis is unclear. A new study now shows that, as non-cell-autonomous drivers, minor cancer cell subclones instigate growth at distant sites of otherwise non-metastatic cancer cells. This is mediated systemically by perturbation in the metastatic tissue.

The ability of cancer cells to adapt to external and internal stresses is critical for tumourigenesis. A new study now shows that the integrated stress response is critical for tumour cell adaptation to stress induced by c-MYC activation, providing mechanistic insights into tumour responses to intrinsic stresses with implications for cancer therapies.

In this Review, the authors survey key advances in stem cell research and describe the cell types that are currently being used in the clinic or are close to clinical trials.

Sigal et al. report that Rspo3 regulates Lgr5 cells in the gastric gland base, induces their differentiation into secretory cells and stimulates epithelial antimicrobial defence against H. pylori infection.

Tian et al. report that the chromatin-related factor Whsc1 regulates the exit from pluripotency and germ layer specification of mouse embryonic stem cells by binding to enhancers of mesendodermal regulators.

Fu et al. report the transition of ESCs into a 2-cell-embyro-like state induced by Dux involves two steps and can be prevented by Myc and Dnmt1, which inhibit the downregulation of pluripotency genes and the activation of 2C⁺-upregulated elements.

Diring et al. identify ArhGAP12 and ArhGAP32 as RPEL proteins that bind G-actin. When bound to G-actin, ArhGAP12 cannot suppress Rac, thus coupling Rac activity to actin availability.

Clancy et al. delineate a pathway for pre-miRNA delivery into nascent extracellular vesicles released from tumour cells and show that shed vesicles contain machinery allowing cell-free pre-miRNA processing.

Senoo et al. show that, in response to chemoattractant stimulation, phosphorylated Rho–GDP in complex with Ras–GTP and mTORC2 promotes AKT phosphorylation to mediate cell migration.

Janiszewska et al. show that minor subpopulations expressing IL11 and FIGF in breast cancer cells promote metastasis through altering local and systemic tumour microenvironments including neutrophils.

Activating transcription factor 4 (ATF4) promotes MYC-driven tumour progression. Tameire et al. identify ATF4 and its target eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) as regulators of MYC-mediated amino acid biosynthesis and protein synthesis, thereby modulating tumour progression and survival in mice.

Simunovic et al. use human embryonic stem cells to generate a three-dimensional model of a human pre-gastrulation epiblast and show that anterior–posterior symmetry breaking can be induced by BMP4 and WNT signalling.