UBE20, a gene found on chromosome 17, may play a role in breast and prostate tumor formation, MD Anderson researchers found in a recent study. This discovery may lead to future therapies targeting the gene.
The study, led by Min Sup Song, Ph.D., assistant professor of Molecular and Cellular Oncology, found that UBE20’s interaction with adenosine monophosphate kinase a2 (AMPKa2) appears to spur tumor formation. AMPKa2 is a subunit of a protein kinase — an enzyme that modifies the function of other proteins by attaching phosphate groups to them. Protein kinases are key controllers of most biochemical pathways and important in health and disease. Over 160 protein kinases play a role in human diseases, and several dozen are the targets of drugs in development or already approved.
The study’s findings build upon a prior discovery that revealed AMPK suppresses the rewiring of metabolism toward glycolytic and biosynthetic pathways in cancer.
“Our study demonstrated that UBE20 and AMPKa2, but not AMPKa1, form a functional axis that elicits pro-growth, glycolytic, and biosynthetic cancer programs,” said Song.
This process is mediated by mTOR-HIF1a. Tumors that form as a result of increased mTOR (mammalian target of rapamycin) are often regulated through hypoxia-inducible factor (HIF)-mediated transcription. The partnership between UBE20 and AMPKa2 are mediated by a specific HIF called mTOR-HIF1a.
Numerous studies have revealed that the mTOR pathway is one of the major growth regulatory pathways controlled by AMPK. Song’s team, using newly generated UBE20 knockout mice, found that UBE20 promoted heightened activation of mTOR signaling, marked by increased phosphorylation in an AMPKa2-dependent manner. The team observed that loss of one or both alleles of UBE20 resulted in delayed tumor growth and metastasis rates in the mouse models.
“While ablation of UBE20 provides a significant anti-tumor effect and survival advantage in mouse models of breast and prostate cancers, inactivation of AMPKa2 appears to reverse the attenuation of tumorigenesis caused by UBE20 loss,” said Song. “The biological and clinical relevance of UBE20 in tumorigenesis suggests that UBE20 may be a promising target for anti-cancer therapeutics.”