A paper from the Di Cunto’s group shows that the PPP4R2 protein is a functional partner of SMN in neuronal differentiation and survival.

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by prenatal and/or perinatal degeneration of spinal motor neurons, caused by mutation of the Survival of Motor Neuron (SMN) gene. One of the outstanding problems of SMA research is to understand by which mechanisms the mutation of SMN, a ubiquitous protein that plays an essential role in the assembly of the splicing machinery, may produce the specific loss of this specialized neuronal population. In this manuscript Ylenia Bosio, Gaia Berto et al. have discovered that PPP4R2, a previously described interactor of SMN, plays a very specific role in the control of neuronal differentiation and survival. Moreover they have found that the interaction with SMN is relevant for these activities. Considering that PPPR2 controls the activity of the protein phosphatase PPP4C, these results suggest that modulating the activity of this target could be used as a strategy to influence the neuronal-specific phenotypes deriving from SMN loss.

A paper of Cavallo’s Immunology Lab (Arigoni et al.) in collaboration with Aime’s Molecular Imaging Group describes a vaccine targeting angiomotin, which alters tumor vessel permeability and hampers the growth of established tumors. 

Agiomotin (Amot) is one of several identified angiostatin receptors expressed by the endothelia of angiogenic tissues. A DNA vaccine targeting Amot overcomes immune tolerance and induces an antibody response that hampers the progression of incipient tumors. Electroporation of plasmid coding for the human Amot (pAmot) significantly delayed the progression both of autochthonous tumors in cancer prone BALB-neuT and PyMT genetically engineered mice and transplantable TUBO tumor in wild-type BALB/c mice. The intensity of the inhibition directly correlated with the titer of anti-Amot antibodies induced by the vaccine. Tumor inhibition was associated with an increase of vessels diameter with the formation of lacunar spaces, increase in vessel permeability, massive tumor perivascular necrosis and an effective epitope spreading that induces an immune response against other tumor associated antigens. These data provide a rationale for the development of novel anticancer treatments based on anti-Amot vaccination in conjunction with chemotherapy regimens.

A paper by A. Lembo et al. (Computational Biology Unit) shows that shorter 3' UTRs correlate with poor prognosis in breast and lung cancer.

Proliferating cells partly escape microRNA-mediated regulation by expressing shorter 3' UTRs, depleted of microRNA binding sites, compared to non-proliferating cells. Using large-scale gene expression datasets, we show that a similar phenomenon takes place in breast and lung cancer: tumors expressing shorter 3' UTRs tend to be more aggressive and to result in shorter patient survival. Genes undergoing 3'UTR shortening in aggressive tumors of the two tissues significantly overlap, and several of them are known to be involved in tumor progression.