A known oncogene previously associated with carcinomas of the breast, liver, ovaries, and colon appears to suppress the growth of melanoma cells, a team of researchers reported recently in Cell Reports.
The FOXQ1 gene is a transcription factor that appears to inhibit the same process in melanoma cells that it promotes in these carcinomas, the researchers wrote.
The invasive and metastatic potential of melanoma cells is determined by their ability to undergo a process that resembles epithelial to mesenchymal transition, which is the route through which carcinomas metastasize, the researchers note. While melanoma is not epithelial in nature, the transition to invasion and metastasis is dependent upon a cadherin switch, the authors explain.
Through a series of experiments, the researchers tried to understand the mechanism of action underlying the way in which FOXQ1 inhibits the E/N cadherin switch in melanoma that it promotes in carcinoma cells.
They found that when FOXQ1 interacts with nuclear ß-catenin and TLE proteins, it is turned into either a transcriptional activator or a repressor, which results in induction or repression of the N-cadherin gene (CDH2).
“I’ve never come across such a dramatic split in how cancer cells can respond to a single gene,” said lead researcher Mikhail Nikiforov, Ph.D., in a press release. “The possible implications for cancer management are quite important. These findings may guide us in the future on how we can avoid use of drugs that, while eliminating one type of cancer, may at the same time induce another.” Dr. Nikiforov is associate professor of oncology in the Department of Cell Stress Biology at Roswell Park Cancer Institute, Buffalo, N.Y.
1. Bagati A, Bianchi-smiraglia A, Moparthy S, et al. Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1. Cell Rep. 2017;20(12):2820-2832. http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31182-8