In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-06-05)
Abstract:
One of the most common cancers in children and adolescents is rhabdomyosarcoma, a cancer of soft tissue such as muscle, tendon or cartilage. The fusion of DNA on two different chromosomes causes the most aggressive form of rhabdomyosarcoma. The fused DNA produces an abnormal protein called PAX3-FOXO1. During normal muscle development, a subset of rapidly growing cells eventually slow down and form mature, working muscle cells. It is still unclear how exactly rhabdomyosarcoma develops, but it is thought that PAX3-FOXO1 stops muscle cells from maturing and the cells that grow out of control result in a tumor. Learning how PAX3-FOXO1 hijacks normal muscle development could lead to new treatments for rhabdomyosarcoma. One treatment approach is to slow the growth of a tumor and force the cells to mature. Then, young patients might avoid chemotherapy or radiation treatments and their side effects. Efforts to improve treatment for this type of cancer face several obstacles. Currently, only one vertebrate animal model of the disease is available to test drugs, and it is still not known how PAX3-FOXO1 causes healthy cells to become cancerous. It is also hard to turn off PAX3-FOXO1 itself, so scientists must find additional proteins that collaborate with it to target with drugs. Now, Kendall et al. show that genetically engineered zebrafish with human PAX3-FOXO1 develop rhabdomyosarcoma-like tumors. Experiments on these zebrafish showed that the protein turns on a gene called her3. Humans have a similar gene called HES3. In zebrafish or mouse cells, human HES3 interferes with muscle-cell maturation and allows cells that acquire PAX3-FOXO1 to persist during development instead of dying. It also increases the cell growth and cancerous behavior in human tumor cells. Kendall et al. further looked at HES3 levels in tumors collected from patients with rhabdomyosarcoma and found that having higher levels of HES3 increased the risk of death from the cancer. Human rhabdomyosarcoma tumors with high HES3 levels were also more likely to have certain cell-growth and cell-differentiation related proteins. Drugs that turn off or modify the activity of these proteins already exist. Testing these drugs that target processes such as cell growth in the zebrafish with rhabdomyosarcoma-like tumors may help scientists determine if they reduce tumor growth. If they do, additional trials could determine if they would help patients with rhabdomyosarcoma.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.33800.001
DOI:
10.7554/eLife.33800.002
DOI:
10.7554/eLife.33800.003
DOI:
10.7554/eLife.33800.004
DOI:
10.7554/eLife.33800.005
DOI:
10.7554/eLife.33800.006
DOI:
10.7554/eLife.33800.007
DOI:
10.7554/eLife.33800.008
DOI:
10.7554/eLife.33800.009
DOI:
10.7554/eLife.33800.010
DOI:
10.7554/eLife.33800.011
DOI:
10.7554/eLife.33800.012
DOI:
10.7554/eLife.33800.013
DOI:
10.7554/eLife.33800.014
DOI:
10.7554/eLife.33800.015
DOI:
10.7554/eLife.33800.016
DOI:
10.7554/eLife.33800.017
DOI:
10.7554/eLife.33800.018
DOI:
10.7554/eLife.33800.019
DOI:
10.7554/eLife.33800.020
DOI:
10.7554/eLife.33800.021
DOI:
10.7554/eLife.33800.031
DOI:
10.7554/eLife.33800.032
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3
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