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This Week in Cancer Discovery: Jun 13, 2012

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In Cancer Discovery this week, researchers in New York and California report that microRNA-23a promotes the transition of colorectal cancer from indolent to invasive disease. The team profiled somatic copy number alterations in noninvasive adenomas and invasive adenocarcinomas from mouse models and identified a recurrent amplicon on mouse chromosome 8 encoding miRNA-23a and -27a, both of which were upregulated in mouse intestinal adenocarcinomas as well as in human colorectal cancer samples and colorectal cancer cell lines. "Functionally, miR-23a promotes the migration and invasion of colorectal cancer cells and stem cells, whereas miR-27a primarily promotes proliferation," the authors write. "We computationally and experimentally validated that metastasis suppressor 1 is a direct miR-23a target and similarly validated that the ubiquitin ligase FBXW7 is a direct miR-27a target."

Also in Cancer Discovery this week, researchers in Italy report that gene signatures associated with medulloblastoma cancer stem cells can be used to predict the molecular classification of human medulloblastoma and identify novel molecular mediators involved in the disease's genesis. The team compared distinct postnatal hindbrain-derived neural stem cells from mouse brains with murine compound Ptch/p53 mutant medulloblastoma cancer stem cells and found that transcriptome analysis of both results in the identification of gene signatures reminiscent of specific human medulloblastoma molecular subclasses. "These data indicate that gene expression analysis of medulloblastoma [cancer stem cells] holds great promise not only for understanding functional differences between distinct [cancer stem cell] populations but also for identifying meaningful signatures that might stratify medulloblastoma patients beyond histopathologic staging," the authors write.

Finally in Cancer Discovery this week, researchers in the US and UK describe a novel mechanism of inducing apoptosis in cancer cells through the inhibition of the protein kinase WEE1. The team shows that WEE1 inhibition forces S-phase-arrested cells into mitosis without letting them complete DNA synthesis. This results in highly abnormal mitoses and, ultimately, mitotic exit and apoptosis. "This mechanism of cell death is shared by CHK1 inhibitors, and combined WEE1 and CHK1 inhibition forces mitotic entry from S-phase in the absence of chemotherapy," the authors write. "We show that p53/p21 inactivation combined with high expression of mitotic cyclins and EZH2 predispose to mitotic entry during S-phase with cells reliant on WEE1 to prevent premature cyclin-dependent kinase (CDK)1 activation." This suggests that WEE1 inhibition could be a targeted therapy for aggressive breast cancer, they add.

The Scan

And For Adolescents

The US Food and Drug Administration has authorized the Pfizer-BioNTech SARS-CoV-2 vaccine for children between the ages of 12 and 15 years old.

Also of Concern to WHO

The Wall Street Journal reports that the World Health Organization has classified the SARS-CoV-2 variant B.1.617 as a "variant of concern."

Test for Them All

The New York Times reports on the development of combined tests for SARS-CoV-2 and other viruses like influenza.

PNAS Papers on Oral Microbiome Evolution, Snake Toxins, Transcription Factor Binding

In PNAS this week: evolution of oral microbiomes among hominids, comparative genomic analysis of snake toxins, and more.