By Michelle Mukonyora
16 February 2016
Cancer is one of the leading causes of death amongst the non-communicable disease in Africa. For African women, breast cancer is the most common cancer. Breast cancer usually becomes lethal when it becomes metastatic, i.e. when it spreads. Approximately only one in five women will survive breast cancer that has metastasized for longer than five years. It is therefore important for us to understand the mechanisms through which cancerous cells become metastatic.
Researchers at the Tumor Microenvironment and Metastasis Program of the Wistar Institute identified 41 genes that are inversely correlated with breast cancer survival. Out of the 41 genes, the GABAA receptor alpha3 (Gabra3) gene was of particular interest because it was previously thought to only be expressed in brain tissue. Secondly Gabra3 is highly expressed in breast cancer tissue but not in healthy tissue. Its gene product is a cell surface protein, which makes the Gabra3 protein easily accessible to drug molecules. It is additionally ideal as a drug target because there are existing drugs that are used to treat neural diseases like alcohol dependence, depression, insomnia and anxiety disorders. There are approximately 58 drugs that are known to bind to Gabra3.
Studies in animal models showed that breast cancer cells that express Gabra3 are better able to migrate within the body and colonize healthy tissues. However, other versions of Gabra3 were shown to do the opposite and actually suppress breast cancer metastasis. This is the result of a regulatory mechanism called RNA editing. RNA is a messenger molecule that passes on the message from genes and facilitates the manufacture of the gene product (Figure 1), which in this case is the cell surface Gabra3 protein. When changes are made to the RNA molecule of a particular gene, the activity or function of the protein can be altered. Associate Professor Qihong Huang and his colleagues found that RNA edited Gabra3 is found only in non-invasive breast cancers.
This is good news because there is a group of molecules called interferons that when present, can increase RNA-editing. Interferon mediated treatments may in future be used to control the spread of metastatic breast cancer as well as existing Gabra3 drug inhibitors.
Read the full article: Gumireddy, K. et al. (2016) The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis. Nature Communications. 7:10715. DOI: 10.1038/ncomms10715