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This Week in Cancer Research: Jul 18, 2012

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In Cancer Research this week, a team from China and the US reports that Fos transcription factor Fra-1 makes breast cancer cells more sensitive to chemotherapy. The team observed a correlation between Fra-1 expression in human stage II breast cancer tissues and levels of clinical chemoresistance. In an in vitro model, the researchers also found that knocking down Fra-1 resulted in breast cancer cells becoming resistant to doxorubicin and cyclophosphamide, whereas increased expression led to chemosensitivity. "The tumor cell side population, which is enriched for cancer stem cells, was found to be associated with chemoresistance," the authors write. "Increased side population fractions were detected among tumor cell lines subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was correlated with a decreased side population fraction, and significantly, this finding was recapitulated in vivo, where tumors with enhanced expression of Fra-1 were found to have blunted growth."

Also in Cancer Research this week, researchers at the University of California, San Francisco, report on the role of miRNA-708 in controlling CD44+ prostate cancer-initiating cells. The microRNA is a negative regulator of this subpopulation of prostate cancer cells and was under-expressed in the CD44+ cells from prostate cancer xenografts studied by the researchers. They also found that reconstitution of miR-708 in prostate cancer cell lines or CD44+ prostate cancer cells leads to decreased tumorigenicity in vitro. "Intratumoral delivery of synthetic miR-708 oligonucleotides triggered regression of established tumors in a murine xenograft model of human prostate cancer," they write. "Conversely, miR-708 silencing in a purified CD44− population of prostate cancer cells promoted tumor growth." Low miR-708 expression correlated with poor survival outcome, tumor progression, and recurrence in patients with prostate cancer. This suggests that reduced expression leads to "prostate cancer initiation, progression, and development by regulating the expression of CD44 as well as AKT2," the team adds.

Finally in Cancer Research this week, researchers in South Korea report that Wnt signaling in cancer suppresses the activity of cytochrome C oxidase and regulates glucose metabolism. Wnt inhibits the expression of COX subunits COXVIc, COXVIIa, and COXVIIc, the team says, adding: "We found that Wnt induced a glycolytic switch via increased glucose consumption and lactate production, with induction of pyruvate carboxylase (PC), a key enzyme of anaplerosis." The researchers also found that shRNA-mediated knockdown of E-cadherin, which regulates epithelial-to-mesenchymal transition, represses mitochondrial respiration and induces a glycolytic switch via Snail activation, "indicating that EMT may contribute to Wnt/Snail regulation of mitochondrial respiration and glucose metabolism."

The Scan

Study Finds Few FDA Post-Market Regulatory Actions Backed by Research, Public Assessments

A Yale University-led team examines in The BMJ safety signals from the US FDA Adverse Event Reporting System and whether they led to regulatory action.

Duke University Team Develops Programmable RNA Tool for Cell Editing

Researchers have developed an RNA-based editing tool that can target specific cells, as they describe in Nature.

Novel Gene Editing Approach for Treating Cystic Fibrosis

Researchers in Science Advances report on their development of a non-nuclease-based gene editing approach they hope to apply to treat cystic fibrosis.

Study Tracks Responses in Patients Pursuing Polygenic Risk Score Profiling

Using interviews, researchers in the European Journal of Human Genetics qualitatively assess individuals' motivations for, and experiences with, direct-to-consumer polygenic risk score testing.