Turning Myc off and on

A team of Australian and Italian researchers have discovered a completely new pathway in which a cell protein causes two common forms of cancer, neuroblastoma and breast cancer.

In neuroblastoma and breast cancer, levels of Myc proteins are commonly elevated in tumour cells. High levels of the protein are also associated with poor treatment outcomes.

However, the way in which these proteins cause cancer has remained unknown.

For the first time, researchers at Children's Cancer Institute Australia for Medical Research (CCIA) and collaborators in Italy describe how the Myc proteins lead to tumour formation.

"Our results show that Myc proteins cause cancer by switching off genes involved in cancer prevention, such as transglutaminase 2 (TG2)," Professor Glenn Marshall, head of CCIA's molecular carcinogenesis program and director of the Centre for Children's Cancer and Blood Disorders at Sydney Children's Hospital, said.

"In addition to this, we have also shown that when the neuroblastoma and breast cancer cells are treated with a new class of anti-cancer drugs called histone deacetylase inhibitors (HDACIs), they are able to turn the TG2 gene back on, which then inhibits tumour growth."

The results, published this week in the US' Proceedings of the National Academy of Science journal, describe in detail the complex interaction between the Myc protein, TG2 gene and HDACI drug within tumour cells.

"This work highlights the importance of HDACIs for the treatment of cancers caused by the high levels of Myc proteins," Marshall said.

"More importantly, we identify TG2 as a potential drug development target for the treatment of these cancers.

"We believe that TG2 mimetics, combined with HDACIs in cancer therapy, will have potent anticancer effects in cells driven by Myc proteins."

Source: CCIA