Disruptive protein opens doors to spread tumours
June 21, 2016
Much like the remote control on a garage door, stathmin sends signals that let cancer cells into and out of blood vessels.
Researchers at Children’s Cancer Institute have found that the protein stathmin helps the childhood cancer neuroblastoma to spread by disrupting cell signals, letting cancer cells gain entry into organs away from the original tumour.
This finding, presented today at the international neuroblastoma research conference, ANR2016, in Cairns and published in the journal Oncogene, paves the way to identify new anti-cancer drugs that target the protein.
This Australian research provides previously unknown information about the important role stathmin has in how neuroblastoma cells spread or metastasise. The research is published online this week in the prestigious journal Oncogene and is being shared with over 400 researchers at the Advances in Neuroblastoma Research Congress (ANR2016) held 19-23 June.
Research leader Professor Maria Kavallaris of Children’s Cancer Institute said that stathmin was known to bind to cell skeletons. However, she and her team found it spreads cancer cells, not by hijacking the cytoskeleton, but by disrupting chemical signals in the cancer cell to create openings in blood vessels that allow tumour cells to spread and to invade new organs.
“Much like the remote control on a garage door, stathmin sends signals that open doors out of and into blood vessels to help neuroblastoma tumour cells spread through the body. This study has provided valuable information to help us find new treatments” she said.
“Advancing our understanding of the metastatic process provides us with opportunities to identify treatment vulnerabilities in the cancer”, she said.
Neuroblastoma is the most common solid tumour of early childhood. In 70 per cent of cases, when it is diagnosed, neuroblastoma has already spread into other organs. That means less than half of patients are still alive five years later.
Metastasis, the spread of cancer cells from one organ to another, is a complex, multistep process. Once a cancer has metastasised, it is much harder to treat. The details of the metastatic process are still largely a mystery.
Stathmin is a protein that binds to the cytoskeleton and helps it rapidly remodel itself in response to cells’ needs. It was thought to make cancer cells more mobile by affecting how they grow and move, and seed to form new tumours at distant sites.
To test how stathmin helps cells spread, the researchers suppressed its production in neuroblastoma cells by switching off the gene that codes for it, then looked to see which processes were affected.
“This research has advanced our understanding of how stathmin alters chemical signals to change neuroblastoma cells’ shape and move through blood vessels. Now we need to see if does the same thing in other cancers”, she said.
The team will present their research at the international conference, Advances in Neuroblastoma Research (ANR2016).
Paper: Christopher M Fife, Sharon M Sagnella, Wee S Teo, Sela T Po’uha, Frances L Byrne, Yvonne YC Yeap, Dominic CH Ng, Thomas P Davis, Joshua A McCarroll, Maria Kavallaris ‘Stathmin mediates neuroblastoma metastasis in a tubulin-independent manner via RhoA/ROCK signaling and enhanced transendothelial migration’, Oncogene 20 June 2016
This research was done in affiliation with UNSW and Sydney Children’s Hospital and was funded in part by Australian Centre for NanoMedicine, Kids Cancer Project, NHMRC and ARC.
The Advances in Neuroblastoma Research Congress, ANR2016, will be held 19-23 June at the Cairns Convention Centre. This meeting will provide a key opportunity for research scientists, clinicians, early career fellows, nurses and other allied health care workers to be updated on the latest basic, translational and clinical research developments in the field of childhood neuroblastoma. There will also be strong engagement of parents and supporters with specific program content. More information at www.anr2016.org.
Neuroblastoma is a childhood cancer of specialised nerve cells which are involved in the development of the nervous system and other tissues. Neuroblastoma can occur anywhere in the body. In some children, neuroblastoma is found in the neck in nerve tissue in the chest, and also around the spinal cord. Like other cancers, no cause has been found. The average age of diagnosis is just 2 years old. Neuroblastoma claims more lives of children under the age of 5 than any other cancer. Over 20 babies and toddlers will die from this disease in Australia this year and a third of survivors will have long term side effects from their treatment. The average survival rate for neuroblastoma is only 50% and the rate for the most aggressive form of neuroblastoma can be as low as 15%. It is the most common solid tumour in early childhood. The cancer can appear in different parts of the body, but it usually occurs in the abdomen (stomach) as a swelling, in the adrenal gland.
About Children’s Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision remains unchanged – to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ more than 220 researchers, operational staff and students, and has established a national and international reputation for scientific excellence.
Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
We are currently leading the establishment of the Zero Childhood Cancer national child cancer personalised medicine program for children with the most aggressive cancers, in partnership with the Sydney Children’s Hospitals Network. This program will revolutionise the way treatment decisions are made, with the aim of improving survivorship for those children at highest risk of treatment failure from their disease.