New insight into critical molecular mechanisms involved in aggressive childhood cancer
One of the most promising new ideas about the causes of cancer, known as the cancer stem-cell model, must be reassessed because it is based largely on evidence from a laboratory test that is surprisingly flawed when applied to some cancers, University of Michigan researchers have concluded. By upgrading the lab test, the U-M scientists
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A new study reveals critical molecular mechanisms associated with the development and progression of human neuroblastoma, the most common cancer in young children.
The research, published by Cell Press in the January 6th issue of the journal Cancer Cell, may lead to development of future strategies for treatment of this aggressive and unpredictable cancer.
Neuroblastoma cells are derived from migratory neural crest cells that give rise to the peripheral sympathetic nervous system. During normal development, neural crest cells stop dividing and differentiate. However, neuroblastoma cells seem to have lost this capacity. Previous work has shown that amplification of the MYCN gene, which disrupts control of cell division and differentiation, is a strong predictor of poor prognosis in neuroblastoma.
“We speculated that genes that are expressed in a MYCN-dependent manner might be required specifically for the growth of MYCN-amplified neuroblastomas and that MYCN-amplified neuroblastomas might depend not only on N-Myc itself, but also on upstream regulatory factors or downstream target genes,” explains senior study author, Dr. Martin Eilers, from the University of Wurzburg in Germany.
Dr. Eilers and colleagues performed a genetic screen of nearly 200 genes that are dependent on amplified MYCN in human neuroblastoma or are direct targets of Myc. The researchers found that the oncogene AURKA is required for growth of MYCN-amplified neuroblastoma cells, but not cells lacking amplified MYCN.
AURKA encodes the kinase Aurora A which is dysregulated in multiple types of cancer cells. Interestingly, Aurora A kinase activity was not required for N-Myc stabilization. Instead, elevated Aurora A levels in MYCN-amplified neuroblastoma cells interfered with the PI3-kinase-dependent and mitosis-specific degradation of N-Myc. This suggests that small molecule inhibitors of Aurora A kinase may not be effective at inhibiting the oncogenic functions of Aurora A.
“Our results show that stabilization of N-Myc is a critical oncogenic function of Aurora A in childhood neuroblastoma; the challenge will now be to find ways to interfere with this function in order to find new approaches for the therapy of these tumors,” says Dr. Eilers. “The findings also suggest that the current views about why Aurora A is oncogenic may need to be re-evaluated.”
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Ovarian cancer cells are “addicted” to a family of proteins produced by the notorious oncogene, MYC. Blocking these Myc proteins halts cell proliferation in the deadliest cancer of the female reproductive system, according to a presentation by University of California, Berkeley scientists at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17,
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Ovarian cancer cells are “addicted” to a family of proteins produced by the notorious oncogene, MYC, and blocking these Myc proteins halts cell proliferation in the deadliest cancer of the female reproductive system, according to a presentation by University of California, Berkeley scientists at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec.
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After identifying an apparent population of cancer stem cells for neuroblastoma, researchers successfully used a reprogrammed herpes virus to block tumor formation in mice by targeting and killing the cells. Published online Jan. 21 by PLoS (Public Library of Science) One, the study led by Cincinnati Children’s Hospital Medical Center adds to a growing body
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In the December 1st issue of G&D, Dr. Fred H. Gage (The Salk Institute for Biological Studies) and colleagues reveal a role for the Hippo signaling pathway in the regulation of vertebrate neural development, identifying new factors - and potential therapeutic targets - that may be involved in congenital brain size disorders and neurological tumor formation. Their
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