Scientists identify potential new neuronal tumour suppressor

Scientists at Dana Farber Cancer Institute have identified a potential new neuronal tumour suppressor.

Washington, March 18 : Scientists at Dana Farber Cancer Institute have identified a potential new neuronal tumour suppressor.

"It has been suspected for decades that the short arm of chromosome 1 harboured one or more tumour suppressor genes because this region is deleted in a variety of tumours, including many neural crest-derived tumours. Our work suggests that KIFB (beta) is one such gene," says Dr. William Kaelin, a Professor in the Department of Medicine at the institute.

Neural crest-derived tumours include the most common malignant paediatric solid tumours like neuroblastomas and medulloblastomas, tumours of the sympathetic nervous system like paragangliomas, and the deadliest form of skin cancer called melanomas.

Dr. Kaelin says that under normal developmental conditions, neural crest cells respond to diminishing growth factor signalling by inducing apoptosis through a pathway involving the enzyme EglN3.

He, however, adds that the acquisition of mutations that enable cells to avoid apoptosis under low growth factor conditions provide a growth advantage, and an effective route to tumorigenesis.

In a study, Dr. Kaelin and his colleagues observed that the protein KIF1B (beta) mediates EglN3-induced neuronal apoptosis, and thereby provides a protective effect against the development of neural crest-derived tumours.

The researchers revealed that KIF1B (beta) is positioned on the region of chromosome 1p that is deleted in a number of neural crest-derived tumours. According to them, the supplementation of 1p-deleted neuroblastoma cancer cells with KIF1B (beta) protein is sufficient to restore apoptosis.

They have even identified inactivating point mutations in neural crest-derived tumours.

The researchers have also shown that partial reduction of KIF1B (beta), but not complete loss, confers protection against apoptosis, something that may help explain why most 1p-deleted tumors still retain the other KIF1B (beta) allele in its normal form.

Dr. kaelin says that further research is needed to delineate the mechanism by which KIF1B (beta) induces apoptosis. He, however, insists that this work opens up several avenues for investigation.

He says that "an intriguing possibility is that an increase in EglN3 activity is responsible for the spontaneous regressions frequently observed in neonates who present with Neuroblastoma (so-called Stage 4S Neuroblastoma). Perhaps, in time, we can mimic this with EglN3 agonists."

The study has been reported in the online edition of the journal G and D.

ANI