Reviews & Analysis

During development, tubular networks form through the joining of lumenized branches. Further insights into tracheal tube fusion in Drosophila melanogaster now reveal the molecular steps that promote the connection of two apical membrane compartments within a single cell through secretory lysosomes.

Although known to induce cellular senescence, an important tumour suppressor mechanism, mutation of CDKN1A — the gene encoding p21 (also known as WAF1 or CIP1) — is rare in human cancers. Now, a study reports a previously unappreciated oncogenic effect of p21 overexpression that shapes cancer genome evolution through induction of replication stress.

Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression.

Sanchez and Dynlacht discuss recent insights into the mechanisms of primary cilia assembly and disassembly, and the relationships between ciliogenesis and cell cycle regulation as well as disease.

Metabolic rewiring is essential for cancer cell survival. PGC1α, a transcriptional co-activator that is downregulated in prostate cancer, is now shown to control prostate cancer metabolism by activating an oxidative metabolic program that prevents tumour growth and metastatic dissemination.

The function and regulation of repetitive DNA, the 'dark matter' of the genome, is still only rudimentarily understood. Now a study investigating DNA replication of repetitive centromeric chromosome segments has started to expose a fascinating replication program that involves suppression of ATR signalling, in particular during replication stress.

The primary cilium and the process of autophagy are thought to be in a functionally reciprocal relationship. In further support of this link, fluid flow sensing by the primary cilium is now shown to induce autophagy, which in turn regulates the volume of kidney epithelial cells.

The skin forms a protective, water-impermeable barrier consisting of heavily crosslinked epithelial cells. However, the specific role of stem cells in sustaining this barrier remains a contentious issue. A detailed analysis of the interfollicular epidermis now proposes a model for how a composite of cells with different properties are involved in its maintenance.

Yau and Rape discuss recent advances in our understanding of the many variations in ubiquitin chain topology and how these mediate ubiquitin-dependent signalling in the cell.

Many biological processes are influenced by the mechanical rigidity of surrounding tissues. Now, a combination of experiments and mathematical modelling has been used to describe the precise molecular and physical mechanism by which cells sense and respond to the mechanical properties of their extracellular environment through integrin-based adhesions.

The liver is the most common metastatic route of pancreatic cancer. Early recruitment of granulin-secreting inflammatory monocytes to the liver is now shown to reprogram hepatic stellate cells into myofibroblasts that modulate the liver microenvironment to support the growth of metastasizing tumour cells.

Contact sites between the endoplasmic reticulum and the plasma membrane mediate receptor signalling. How this function is controlled physically and functionally is poorly understood. Extended synaptotagmins are now shown to shuttle the lipid metabolite diacylglycerol from the plasma membrane to the endoplasmic reticulum in receptor-stimulated cells.

Wnt/β-catenin signalling is an important regulator of liver development, zonation and regeneration. The cell surface complex RSPO–LGR4/5–ZNF3/RNF43 is now shown to direct Wnt/β-catenin signalling in orchestrating the division of the liver into functionally distinct metabolic zones, providing insights into the mechanisms that influence organ development and regeneration.

A powerful combination of cell labelling, genetic tools and rapid imaging techniques in vivo has now led to a high-resolution description of lumen formation during angiogenesis in zebrafish. The study reveals a haemodynamic-force-driven and myosin-II-dependent cellular mechanism (termed inverse membrane blebbing) as the basis for lumen expansion in unicellular and multicellular angiogenic sprouts.

Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation.

LaGory and Giaccia discuss the effects of hypoxia and its downstream responses in cancer and stromal cells.

Visvader and Clevers discuss how stem cells from different tissues, such as the intestine, mammary gland and skeletal muscle, follow different strategies and hierarchies to maintain their complex, tissue-specific balance.

Broken ends of a budding yeast chromosome exhibit increased mobility, presumably to facilitate repair by recombination. A new study reports that increased mobility reflects the untethering of the broken chromosome, triggered by a DNA damage response that phosphorylates the Cep3 kinetochore protein and weakens the association between the centromere and the spindle pole body.

Transporting epithelia commonly consist of tubes that mediate between the body and its environment. Lumen formation is closely linked to epithelial morphogenesis, but an open question is how luminal symmetry is broken to generate tubes rather than hollow cysts. A report about the biomechanics of intercellular contacts might now provide some answers.

Sander and colleagues discuss recent evidence for and against the roles of stem cells versus the plasticity of mature cell types in response to injury during regeneration of the adult liver and pancreas.