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This Week in PNAS: Mar 1, 2011

In this week's PNAS Early Edition, investigators at the University of Edinburgh in the UK show that "transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer." More specifically, in its investigation of promoter methylation in 19 breast cancer cell lines and 47 primary breast tumors, the team found "120 genes that were significantly repressed in association with methylation," which "allowed the unsupervised segregation of cell lines into epithelial and mesenchymal lineages." The Edinburgh team says that aberrant methylation is a marker for cell lineage rather than for tumor progression.

An international research team this week reports the small molecule antibacterial enoxacin, and its role as a "cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing." Enoxacin, the team shows, promotes the production of miRNAs that act as tumor suppressors in human cell cultures as well as xenografted, orthotopic, and metastatic mouse models.

Researchers at the University of California, San Francisco, along with their international collaborators, report on the role of progranulin gene in neurodegeneration. In a nematode model, the team characterized the typical functions of progranulin; C. elegans mutants lacking the gene that encodes progranulin showed a more rapid clearance of apoptotic cells. "Although most neurodegenerative diseases are thought to be caused by the toxic effects of aggregated proteins, our findings suggest that susceptibility to neurodegeneration may be increased by a change in the kinetics of programmed cell death," the authors write in PNAS.

Also in this week's PNAS, a trio of investigators at Stanford University presents a proteomics-based approach, based on the identification of multiple cargo-binding proteins, to investigate the functions of Drosophila myosin VI. Using mass spec techniques in this manner, the team found "a number of … binding proteins, and further characterization of their interactions with myosin VI will advance our understanding of the roles of these complexes in cellular and developmental processes."