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This Week in PNAS: Sep 18, 2018

In the early, online version of the Proceedings of the National Academy of Sciences, a University of California, Los Angeles-led team describe proteolytic enzymes secreted by circulating tumor cells (CTCs). Using a microfluidics-based approach, the researchers isolated cells from cancer cell lines and CTCs from seven individuals with metastatic, castration-resistant prostate cancer to quantify levels of metalloprotease enzyme activity. "We reveal an intriguing correlation between CTC protease activity and metastatic progression," the authors report. "Such functional liquid biopsy approaches provide avenues to understand the metastatic process and potential for companion diagnostics."

Italian researchers present a cancer case involving both MET oncogene amplification and a downstream BRAF-activating mutation. The team focused on tumor material from a 64-year-old patient with cancer of unknown primary origin, using panel sequencing, mouse xenografts models, and other approaches to characterize the MET- and BRAF-mutated tumor, which was resistant to single agent targeted therapy. The authors note that "pharmacological blockade of BRAF had no effect, as it was followed by MET reactivation," in a mouse xenograft of a metastatic tumor from the patient, with their follow-up experiments pointing to "the existence of a previously unknown negative feedback inhibition of MET by BRAF."

A research team from the Francis Crick Institute, Imperial College London, and elsewhere retraces the evolution of Fv1, a retroviral restriction factor that mice use to bind capsids from exogenous and endogenous retroviruses. The investigators used phylogenetics to consider the Fv1 sequences in Mus, Apodemus, and other genera from the Muroidea superfamily rodents, putting the estimated age of Fv1 at roughly 45 million years old. "Regions of Fv1 adapt cooperatively," they note, "highlighting its preference for repeated structures, and suggesting that this functionally constrained aspect of the retroviral capsid lattice presents a common target in the evolution of intrinsic immunity."