Volume 16 Issue 6, June 2014

Puisieux et al. discuss endothelial to mesenchymal transition (EMT)-inducing transcription factors in tumorigenesis. They explore how EMT contributes not only to tumour progression through its roles in invasion and metastasis, but also to malignant transformation and early tumour development by impinging on tumour suppressive pathways and cell differentiation states.

The degradation of dysfunctional proteins and organelles by autophagy is important for cell viability. Dikic and co-authors discuss how cargo selection is achieved during selective autophagy and how the processes involved in cargo delivery are related to membrane trafficking pathways.

Pluripotent embryonic stem cells (ESCs) can be derived from blastocyst-stage mouse embryos. However, the exact in vivo counterpart of ESCs has remained elusive. A combination of expression profiling and stem cell derivation identifies epiblast cells from late-stage blastocysts as the source, and functional equivalent, of ESCs.

Despite the widespread occurrence of aneuploidy in cancer cells, the molecular causes for chromosomal instability are not well established. Cyclin B2 is now shown to control a pathway — involving the centrosomal kinases aurora A and Plk1 and the tumour suppressor p53 — the alteration of which causes defective centrosome separation, aneuploidy and tumour development.

Clathrin-independent endocytosis removes membrane receptors and other proteins from the cell surface, yet the mechanisms controlling this process remain unclear. Galectin-3 is now shown to regulate the biogenesis of a subpopulation of clathrin-independent carriers (CLICs). Galectin-3 binds to glycosylated cargo proteins and interacts with membrane glycosphingolipids to induce membrane deformation and CLIC formation.

Cadherin-containing cell–cell junctions respond to intercellular tension by increasing their size, strength and complexity. The mechanical regulation of cadherin adhesions is now shown to involve myosin-dependent tension in the cortical actomyosin cytoskeleton. This reduces actin turnover to decrease the mobility of cadherin molecules and increase their concentration at junctions.

It has been unclear at which stage of mouse development embryonic stem cells can be derived. Nichols and colleagues use single-cell cultures to demonstrate that derivation of cells able to proliferate without ERK signalling (a characteristic of ESCs) is limited to the early pre-implantation epiblast and is favoured by culture on a laminin substrate.

The Par polarity proteins are involved in regulating asymmetric division in stem cells in the fly. Macara and colleagues identify a PAR3 homologue that is expressed in multipotent stem cells in terminal end buds of the murine mammary gland, and is necessary for stem cell maintenance through its effect on Lkb1 kinase activity.

Nam and van Deursen find that overexpression of either cyclin B1 or cyclin B2 in mice causes tumorigenesis and aneuploidy. They show that increased levels of these proteins lead to distinct chromosome segregation defects, and they identify a role for cyclin B2 in centrosome separation.

In the presence of incorrectly segregated chromosomes, the Aurora-B-dependent abscission checkpoint prevents the final stage of cytokinesis. Stenmark and colleagues identify a role for the previously uncharacterized protein ANCHR at the checkpoint, where it acts in an Aurora-B-dependent manner to retain the ATPase VPS4 at the midbody.

Wittmann and colleagues demonstrate that the turnover of mature focal adhesions is regulated by CLASP proteins. They show that CLASP recruitment to focal adhesions is involved in localized exocytosis and extracellular matrix degradation, suggesting that local matrix metalloprotease secretion might promote focal adhesion disassembly.

Hodgson and colleagues use a Rac1 biosensor to delineate a signalling pathway that promotes invadopodia dissolution through the activities of the Rac1 GEF Trio, Rac1 and the Pak1 kinase.

Thiery, Viasnoff and colleagues study the roles of myosin contractility and actin dynamics in regulating the recruitment of E-cadherin at adherens junctions, using an assay that allows live 3D imaging of the intercellular contact of a suspended cell doublet.

Many cell surface receptors are internalized by clathrin-independent endocytosis, but how clathrin-independent carriers (CLICs) are generated at the plasma membrane remained unclear. Johannes and colleagues now report that galectin-3 (Gal3) binds to glycosylated cargo proteins and glycosphingolipids. These interactions induce membrane deformation, revealing a mechanism for CLIC biogenesis.

The zebrafish trunk has a repetitive pattern of dark stripes and light interstripes, arising from the distribution of distinct pigment cells. Nusslein-Volhard and colleagues have traced clones of pigment cells to show that iridophores forming the interstripes emerge from the dorsal root ganglia into the myoseptum, from where they proliferate and spread. The melanophores themselves appear in situ in between these regions to form the stripes.

Jones and colleagues combine lineage tracing experiments, chemical carcinogenesis assays and mathematical modelling to study field change development in a preneoplastic epithelium. They demonstrate that Notch pathway inhibition in oesophageal epithelial progenitor cells results in imbalanced differentiation, and mutant clone expansion and dominance in the epithelium, increasing the likelihood of transformation.