Science this week presents a special issue to mark the 40th anniversary of the signing of the US National Cancer Act in 1971 by then-President Richard Nixon. In their introduction to the special issue, Paula Kibertsis and Eliot Marshall note that papers published in Science at the time were asking questions like, "How do abnormalities in chromosome number arise in tumor cells? Can tissue-specific markers be used to determine the epithelial versus mesenchymal origin of a solid tumor? … Do viruses play a role in human cancer?" Though there are still many questions surrounding cancer, Kibertsis and Marshall say, some have been answered. See the rest of Science's 40th anniversary coverage here.
Also in Science this week, an international team of researchers says mutations in the RNA granule component TDRD7 cause cataract and glaucoma. The researchers present two human cases of pediatric cataract with loss-of-function mutations in TDRD7, and suggest that Tdrd7 nullizygosity in mouse causes cataracts, as well as glaucoma and an arrest in spermatogenesis. "TDRD7 is a Tudor domain RNA binding protein that is expressed in lens fiber cells in distinct TDRD7-RGs that interact with STAU1-ribonucleoproteins," the authors write. "TDRD7 co-immunoprecipitates with specific lens messenger RNAs and is required for the posttranscriptional control of mRNAs that are critical to normal lens development and to RG function."
In Science Signaling this week researchers in Massachusetts present an in vivo systems analysis identifying spatial and temporal aspects of the modulation of TNF-α-induced apoptosis and proliferation by MAPKs. To determine a method of multivariate analysis of cellular responses to external stimuli that would work in vivo as well as in vitro, the researchers analyzed the signaling network that determines the response of intestinal epithelial cells to tumor necrosis factor-α. They found that the extracellular signal–regulated kinase signaling axis was a critical modulator of the temporal variation in apoptosis at different doses of TNF-α and of the spatial variation in proliferation in distinct intestinal regions. "Inhibition of MEK, a mitogen-activated protein kinase kinase upstream of ERK, altered the signaling network and changed the temporal and spatial phenotypes consistent with model predictions," the researcher write. "This study lays a foundation for the use of systems-based approaches to understand how dysregulation of the cellular network state underlies complex diseases."
And finally in Science Translational Medicine this week, researchers in New York say breast cancer methylomes establish an epigenetic foundation for metastasis. The researchers used a genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behaviors, and found that a breast CpG island methylator phenotype was a determinant of metastatic potential. "Specifically, the presence of the B-CIMP in tumors was associated with low metastatic risk and survival, and the absence of the B-CIMP was associated with high metastatic risk and death," the authors write.