Researchers show how in mice the elimination of the Cdh1 protein —a sub-unit of the APC/C complex, involved in the control of cell division—prevents cellular proliferation of rapidly dividing cells.
The researchers are from laboratory of Marcos Malumbres, who is head of the Spanish National Cancer Research Centre's (CNIO) Cell Division & Cancer Group, working alongside Isabel Farińas' team from the University of Valencia.
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Malumbres's group had previously discovered that the inactivation of another APC/C protein, Cdc20, prevented cell division. These results caught the attention of pharmaceutical companies, who are already developing the first inhibitors from the complex. These molecules have caused controversy due to the possible side effects of blocking Cdh1, which is considered a tumour suppressor.
![Aggressive Leukemia Might Be Fueled By Tumor Suppressor: Study]( "Aggressive Leukemia Might Be Fueled By Tumor Suppressor: Study")
Blocking a protein normally credited with suppressing leukemia may be a promising therapeutic strategy for an aggressive form of the disease called acute myeloid leukemia (AML), suggests research.
Manuel Eguren has analysed the biological consequences of Cdh1 elimination in rapidly dividing cells, as part of his doctoral research project in Malumbres's group; he focused on progenitors from the nervous system during embryonic development in mice.
Via a detailed biochemical and cell study, researchers have discovered that the absence of Cdh1 causes DNA damage in cells. This defect causes cell death and leads to alterations in the development of the nervous system such as hydrocephalus, characterised by abnormal accumulation of fluid on the brain.
"Our results solve the controversy about the possible side effects of APC/C inhibitors", says Malumbres, adding that: "we have shown in vivo that their elimination leads to the death of rapidly dividing cells".
IMPLICATIONS FOR TUMOUR TREATMENT
The study is now focused on proposing a precise strategy for specific tumour types. "It could work in glioblastomas given that our study is based on brain progenitors, but we believe it could be extended to include other tumour types", say the researchers.
The CNIO researchers show that cell defects caused by the inhibition of Cdh1 are independent of the presence of the p53 molecule, which is mutated in different types of tumours. "The therapeutic effect of inhibiting Cdh1 should even work in tumours that carry mutations in this molecule", says Malumbres.
Source: Eurekalert
Aggressive Leukemia Might Be Fueled By Tumor Suppressor: Study
Blocking a protein normally credited with suppressing leukemia may be a promising therapeutic strategy for an aggressive form of the disease called acute myeloid leukemia (AML), suggests research.
Advertisement
Manuel Eguren has analysed the biological consequences of Cdh1 elimination in rapidly dividing cells, as part of his doctoral research project in Malumbres's group; he focused on progenitors from the nervous system during embryonic development in mice.
Via a detailed biochemical and cell study, researchers have discovered that the absence of Cdh1 causes DNA damage in cells. This defect causes cell death and leads to alterations in the development of the nervous system such as hydrocephalus, characterised by abnormal accumulation of fluid on the brain.
"Our results solve the controversy about the possible side effects of APC/C inhibitors", says Malumbres, adding that: "we have shown in vivo that their elimination leads to the death of rapidly dividing cells".
IMPLICATIONS FOR TUMOUR TREATMENT
The study is now focused on proposing a precise strategy for specific tumour types. "It could work in glioblastomas given that our study is based on brain progenitors, but we believe it could be extended to include other tumour types", say the researchers.
The CNIO researchers show that cell defects caused by the inhibition of Cdh1 are independent of the presence of the p53 molecule, which is mutated in different types of tumours. "The therapeutic effect of inhibiting Cdh1 should even work in tumours that carry mutations in this molecule", says Malumbres.
Source: Eurekalert
Tumor Suppressor Gene Involved in Acute Myeloid Leukemia Discovered
University of Chicago Medicine Comprehensive Cancer Center (UCCCC) scientists have discovered the tumor suppressor gene involved in acute myeloid leukemia.
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 Tumor Suppressor Needed for Neural Tumour Cells to Mature into NeuronsPreviously, CHD5 was proposed as a tumour suppressor, which acts as a brake that prevents healthy cells from developing into cancer cells. | Advertisement
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