New genetic pathway found responsible for tumor growth

Cancer is the second leading cause of death in the United States and one of the top 10 in the world. The fight against it has so far been long, hard fought, and research intensive. A recent study from Rutgers and Columbia, however, has major implications for treating a kind of cancer called tuberous schlerosis complex (TSC) and may advance the broader world of cancer research (1).

TSC is a rare disease which causes tumors grow on the vital organs (1). Previously, it was thought to be caused by mutations affecting the mTOR pathway – a chain of interactions between genes (2). The mTOR pathway, which stimulates cell growth, becomes overly active active as a result of mutations to the TSC2 gene (2). The HMGA2 gene, however, which produces transcription factors that stimulate the expression of genes, was also known to be highly involved in TSC (2). As a result, Jeanine D’Armiento, the director of the Center for Pulmonary Disease at Columbia University’s College of Physicians and Surgeons, and her associates decided to experiment with both of these mutations in mice (2).

Three different groups of mice were created, all with one functional and one mutant copy of TSC2, and each with a different level of mutation in HMGA2 (2). One group had two normal copies, a second had one mutated and one normal copy, and a third had two mutated copies of HMGA2 (2). Tumor growth in the groups was then examined over a 16-month period (2). Over the course of this period, it became evident that mice without a functional copy of HMGA2 were far less likely to have a tumor, despite possession of the TSC2 mutation (2).

In fact, the HMGA2 protein was found in all the tumors that grew in any group of mice, leading to the conclusion that HMGA2 activity was necessary for tumor growth in TSC (1, 2). Thus, this study overturned previous findings that mutations in the mTOR pathway were key to TSC (1, 2).

In the future, this research may allow for entire new lines of drugs for TSC treatment, which would suppress the HMGA2 gene to prevent tumor growth (1). These findings may also be extended to the analysis and treatment of other kinds of cancer, meaning this research has wide implications for cancer therapies (1).

References:

1. Rutgers Robert Wood Johnson Medical School. (2016, February 17). Cancer study is ‘paradigm shift’ in cause of tumor formation. ScienceDaily. Retrieved from: www.sciencedaily.com/releases/2016/02/160217113640.htm
2. D’Armiento, J., Shiomi, T., Marks, S., Geraghty, P., D’Armiento, J., Shiomi, T., Marks, S., Geraghty, P., Sankarasharma, D., & Chada, K. (2016). Mesenchymal Tumorigenesis Driven by TSC2 Haploinsufficiency Requires HMGA2 and Is Independent of mTOR Pathway Activation. Cancer Research, 76(4), 844-854. doi: 10.1158/0008-5472.CAN-15-1287