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The formation and guidance of specialized endothelial tip cells is essential for both developmental and pathological angiogenesis. Notch-1 signalling regulates the generation of tip cells, which respond to gradients of vascular endothelial growth factor (VEGF-A). The molecular cues and signalling pathways that control the guidance of tip cells are poorly understood. Bidirectional signalling by Eph receptors and ephrin ligands represents one of the most important guidance cues involved in axon path finding. Here we show that ephrin-B2 reverse signalling involving PDZ interactions regulates endothelial tip cell guidance to control angiogenic sprouting and branching in physiological and pathological angiogenesis. In vivo, ephrin-B2 PDZ-signalling-deficient mice (ephrin-B2ΔV) exhibit a reduced number of tip cells with fewer filopodial extensions at the vascular front in the mouse retina. In pathological settings, impaired PDZ signalling decreases tumour vascularization and growth. Mechanistically, we show that ephrin-B2 controls VEGF receptor (VEGFR)-2 internalization and signalling. Importantly, internalization of VEGFR2 is necessary for activation and downstream signalling of the receptor and is required for VEGF-induced tip cell filopodial extension. Together, our results suggest that ephrin-B2 at the tip cell filopodia regulates the proper spatial activation of VEGFR2 endocytosis and signalling to direct filopodial extension. Blocking ephrin-B2 reverse signalling may be an attractive alternative or combinatorial anti-angiogenic therapy strategy to disrupt VEGFR2 function in tumour angiogenesis. [ABSTRACT FROM AUTHOR]

At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic—and some say unethical—events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer. [ABSTRACT FROM AUTHOR]

Reports on a study of the receptor for advanced glycation end products (RAGE), which is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Interaction with molecules implicated in diabetes and Alzheimer's disease; Findings which demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumors and tumors developing spontaneously in susceptible mice.

The article focuses on the bioinformatics tool Tumor Suppressor & Oncogene Explorer for mining large data sets such as Cancer Genome Atlas, developed by geneticist Stephen Elledge and others in 2013. Topics discussed include suggestion of German biologist Theodor Boveri that the aneuploidy, abnormal number of chromosomes, seen in cancer can drive tumour growth. Also presents views of pathologist Megan McNerney, computer scientist Manish Parashar, and breast-cancer specialist Clifford Hudis.

The article focuses on a study which shows that disturbing enzyme pyruvate kinase (PK) in cancer cells can restrain tumour growth in mice. It says that the reduced expression of PKM2 isoform reduces enzyme activity and tumour growth. It states that PKM2 stimulation may lessen the macromolecular precursor availability, thus weaken tumour growth.

The article discusses the study conducted by Raghu Kalluri and his colleagues regarding the structural support provided by tumour cells like pericytes to slow down tumour growth.

The article discusses the tumour suppressor p53 in human cancer therapy. It relates the study by D. M. Feldser and colleagues, and M. R. Junttila and colleagues regarding the restoration of p53 activity which affects only the advanced tumours in mouse models of non-small-cell lung cancer (NSCLC); however cells with early-lesion features are still present in the animals after reactivation. It mentions that p53 activity restoration should have an effect on human tumours.

The article discusses the impact of cellular senescence in preventing the growth and development of tumor cells. It cites two studies which examine the molecular mechanisms that underlies cancer-associated senescence. It mentions that H.-K. Lin conducted an experimental mouse model which reveals the sensitivity of rasconcoprotein to senescence during the absence of Skp2. Meanwhile, the study by S. Campaner and colleagues focuses on cyclin-dependent kinase (CDK2)-deficient mice.

This article discusses research that discovered a molecular compound that inhibits the enzyme NEDD8-activating enzyme (NAE), effectively suppressing the growth of human lung-tumour tissue that has been implanted in mice. This study is pertinent, as it is difficult to find proteins that react to drug treatments. The process of protein degradation within cells wherein small protein ubiquitin is involved in the generation of proteasomes is examined. This research provides insight into the potential for neddylation to be inhibited and whether or not this will affect the growth of tumours.

Reports on the identification of the proteins receptor for advanced glycation end products (RAGE) and amphoterin as regulators in the invasiveness, growth and movement of tumor cells. Implications of the amphoterin and RAGE localization at the edge of neurites during embryonic development for pathological processes such as cancer invasion; How the proteins suppress tumor growth; Potential uses for the RAGE-amphoterin pathway in signal-transduction therapy.

Discusses a report by R.M. Pitti of a newly discovered mechanism that tumors use to avoid a death signal. Details about the production of a soluble molecule which binds to, and neutralizes, a trigger for apoptosis; Possibilities to explain how Fas ligand (FasL) restricts tumor growth.

The article discusses a research work of Raghu Kalluri and colleagues on non-cancerous cells found in connective tissues that surround a tumour in a mouse model of pancreatic cancer which help the immune system to fight the tumour , and mentions work of other researcher Kenneth Olive on the same.