BC Cancer Agency scientists, led by Dr. Poul Sorensen, have discovered a novel gene that suppresses the growth of human tumours in multiple cancers, including breast, lung, and liver cancers, as well as melanomas, lymphomas and sarcomas.
Published in the advance online publication of Nature Medicine, the study found that a gene, HACE1, has the ability to help cells deal with various forms of stress, including environmental cancer triggers that cause tumour formation. When the HACE1 gene is missing or inactive, cancerous cells are able to form tumours, and when the gene is re-expressed, it prevents these cells from forming tumours.
The study was conducted in collaboration with Dr. Josef Penninger of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences.
“The discovery of this gene is very exciting because it clearly impacts a wide range of cancers, and provides a novel link between cellular stress and cancer,” says Dr. Sorensen, Senior Scientist at the BC Cancer Agency, an agency of the Provincial Health Services Authority. “If we can learn how to reactivate HACE1 or block cancer cells from inactivating this gene, it may be possible to improve treatments for many cancer patients.”
To test whether HACE1 is a tumour suppressor gene, researchers knocked out the gene in mice. They hypothesized that the mice would be more susceptible to tumour growth, and diverse tumours did indeed form but at a low rate. However, when the mice were also subjected to various forms of stress, including ultraviolet radiation, lung carcinogens, or other genetic alterations, this resulted in a dramatic increase in cancer growth, with the mice developing breast, lung, and liver cancers, as well as lymphomas, melanomas and sarcomas.
Researchers also re-introduced the HACE1 gene into human tumour cells and found that cells lost their ability to form tumours. Conversely, when levels of HACE1 were experimentally reduced in non-cancerous cells, they were able to form tumours.
“We’ve always suspected that cancer is caused by a combination of genetic and environmental factors working together,” says Dr. Sorensen. “Our results give us insight into how the disease takes root when a single gene is inactivated.”
The next step is to study the biological mechanism that enables HACE1 to deal with cancer stress and block tumour formation.
Core support for research at the BC Cancer Agency is provided by the BC Cancer Foundation. Support for this research project was also provided by the National Cancer Institute of Canada, the Children’s Oncology Group, and the Johal Endowed Chair in Childhood Cancer Research through the BC Children’s Hospital Foundation.
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