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This Week in Cancer Cell: Jul 10, 2012

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In Cancer Cell this week, researchers in California and Canada report that VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Through the enhanced recruitment of the protein tyrosine phosphatase 1B to a MET/VEGFR2 heterocomplex, VEGF regulates tumor cell invasion by suppressing HGF-dependent MET phosphorylation and tumor cell migration, the team writes. "Consequently, VEGF blockade restores and increases MET activity in [glioblastoma multiforme] cells in a hypoxia-independent manner, while inducing a program reminiscent of epithelial-to-mesenchymal transition highlighted by a T-cadherin to N-cadherin switch and enhanced mesenchymal features," the add. They also found that by inhibiting MET in a mouse model of glioblastoma, they could block mesenchymal transition and invasion, resulting in high survival rates.

Also in Cancer Cell this week, researchers in the US and Europe report that the ALKF1174L mutation in neuroblastoma enhances the oncogenic activity of MYCN. The team generated a mouse model that over-expresses ALKF1174L, and compared its activity alone to the activity of MYCN. They found that co-expression of the two oncogenes led to earlier onset of neuroblastoma, higher penetrance, and higher lethality. "ALKF1174LM/MYCN tumors exhibited increased MYCN dosage due to ALKF1174L-induced activation of the PI3K/AKT/mTOR and MAPK pathways, coupled with suppression of MYCN pro-apoptotic effects," the team writes. "Combined treatment with the ATP-competitive mTOR inhibitor Torin2 overcame the resistance of ALKF1174L/MYCN tumors to crizotinib."

Finally in Cancer Cell this week, researchers in Taiwan report that the inhibition of thymidylate kinase in tumor cells allows the enzyme dUTP to be incorporated during DNA double-strand break repair. "Disrupting [ribonucleotide reductase] recruitment to damage sites or reducing the expression of the R2 subunit of RNR prevents the impairment of DNA repair by TMPK intervention, indicating that RNR contributes to dUTP incorporation during DSB repair," the team writes. "We identified a cell-permeable nontoxic inhibitor of TMPK that sensitizes tumor cells to doxorubicin in vitro and in vivo, suggesting its potential as a therapeutic option."

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Nature Papers Describe Gut Viruses, New Format for Storing Quantitative Genomic Data, More

In Nature this week: catalog of DNA viruses of the human gut microbiome, new dense depth data dump format to store quantitative genomic data, and more.