Newly Identified Protein May Provide a Target for MYC Oncogene Activity in Several Cancers
Researchers identified a protein that is essential for MYC to cause cancer in mouse models, and they believe, could be a target for anticancer therapy. The paper, published in Nature Communications (doi:10.1038/ncomms10153), describes the use of genome-wide data analysis techniques to study the behavior of MYC in networks that consist of hundreds of genes.
The MYC oncogene intervenes in many types of cancer, some of which are very aggressive. Researchers suspect that controlling its activity could open avenues to new treatments. But, MYC is an especially complex oncogene and has resisted therapeutic manipulation to date.
MYC is a protein that regulates gene expression in cells. Most proteins act on less than 1% of the genes in the genome, but MYC regulates 2000 to 3000 genes, which is up to 15% of the genes in the entire genome. Consequently, MYC intervenes in a plethora of cellular functions: cellular growth, proliferation, differentiation, and apoptosis.
"MYC is really a general controller of cell activity; it is one of the few genes that, if eliminated, makes cells unviable," explained coauthor Paco Real, MD, PhD, head of the Epithelial Carcinogenesis Group at the Spanish National Cancer Research Centre (CNIO).
When deregulated, MYC promotes the development of several types of cancer (eg, pancreatic, ovarian, and colon cancers, and lymphomas). The MYC gene is altered in more than half of human cancers and is often associated with very aggressive tumors.
For this reason MYC is a sought-after target, with the idea that inhibiting it would constitute a new way of fighting cancer. However, the complicated manner in which it operates makes this oncogene a difficult target.
The CNIO Epithelial Carcinogenesis Group resorted to a genome-wide data analysis strategy. Working with cells cultured in vitro and bioinformatic tools, the researchers managed to identify a gene, BPTF, as a potentially important gene in cancer.
The researchers also detected mutations in BPTF in patients with bladder cancer, and subsequently showed that when BPTF is made inactive, cells are unable to grow suggesting a function related with MYC.
As Real explained, "We saw that when we perturbed the function of BPTF, this affected many genes that are known to depend on MYC; this led us to think that MYC needs BPTF for its biological functions."
Indeed, in a mouse model of pancreatic cancer dependent on MYC, Real's group, in collaboration with the CNIO Molecular Cytogenetics Unit, headed by Juan Cruz Cigudosa, MD, PhD, showed that inhibiting the action of BPTF reduces the aggressiveness of the tumors.
BPTF, therefore, appears as an important link in the chain of molecular events that allow MYC to function. The study showed that by blocking BPTF, tumor cells do not proliferate or their proliferation is reduced; therefore, the researchers considered that this gene could be a new target for treatment in many types of cancer. They suggest targeting the interaction between MYC and BPTF with small molecules.