New insight into aggressive childhood cancer

January 5, 2009

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."

Source: Cell Press

Explore further: In the lab and in the clinic, alisertib with TAK-228 excels against solid tumors

Related Stories

In the lab and in the clinic, alisertib with TAK-228 excels against solid tumors

November 1, 2017
Two University of Colorado Cancer Center studies were presented this weekend at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting in Philadelphia, PA showing that using the drug alisertib along with the ...

Discovery upends model for how dividing cells monitor equal distribution of their chromosomes

April 21, 2013
Ludwig researchers Arshad Desai and Christopher Campbell, a post-doctoral fellow in his laboratory, were conducting an experiment to parse the molecular details of cell division about three years ago, when they engineered ...

Breakthrough in understanding lung cancer vulnerabilities points the way to new targeted therapy

October 1, 2012
More effective treatments for one of the deadliest forms of cancer are one step closer thanks to groundbreaking research from an international collaborative study.

Cancer hijack

July 19, 2013
Genetically unstable breast cancer cells appear to hijack a mechanism used by healthy stem cells to determine how they should develop into different tissues, according to new research.

Does lactate, the bane of athletes, help drive cancer?

March 15, 2017
For decades, lactate has been studied largely in the context of exercise, painted as a nagging metabolic byproduct that accumulates in the tissues and blood during workouts, stiffening muscles and hindering performance.

Research holds promise for personalized lung cancer treatments

January 12, 2017
New research from scientists at Huntsman Cancer Institute (HCI) at the University of Utah uncovered distinct types of tumors within small cell lung cancer that look and act differently from one another. Scientists also identified ...

Recommended for you

Encouraging oxygen's assault on iron may offer new way to kill lung cancer cells

November 22, 2017
Blocking the action of a key protein frees oxygen to damage iron-dependent proteins in lung and breast cancer cells, slowing their growth and making them easier to kill. This is the implication of a study led by researchers ...

One-size treatment for blood cancer probably doesn't fit all, researchers say

November 22, 2017
Though African-American men are three times more likely to be diagnosed with a blood cancer called multiple myeloma, most scientific research on the disease has been based on people of European descent, according to a study ...

One in four U.S. seniors with cancer has had it before

November 22, 2017
(HealthDay)—For a quarter of American seniors, a cancer diagnosis signals the return of an old foe, new research shows.

Combination immunotherapy targets cancer resistance

November 22, 2017
Cancer immunotherapy drugs have had notable but limited success because in many cases, tumors develop resistance to treatment. But researchers at Yale and Stanford have identified an experimental antibody that overcomes this ...

Researchers discover specific tumor environment that triggers cells to metastasize

November 21, 2017
A team of bioengineers and bioinformaticians at the University of California San Diego have discovered how the environment surrounding a tumor can trigger metastatic behavior in cancer cells. Specifically, when tumor cells ...

New study points the way to therapy for rare cancer that targets the young

November 21, 2017
After years of rigorous research, a team of scientists has identified the genetic engine that drives a rare form of liver cancer. The findings offer prime targets for drugs to treat the usually lethal disease, fibrolamellar ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.