A mitogen-activated protein kinase (MAP) known as p38 appears to show promise for halting breast cancer metastasis, and may point to the potential for p38 inhibitors as anti-metastatic agents, according to a study recently published in the June issue of Oncogene.
Sendurai Mani, Ph.D., associate professor of Translational Molecular Pathology, found that the enzyme, while having little to no effect on primary tumor growth, was found to “significantly impede metastasis.”
More than 90% of cancer-related deaths are attributed to metastasis. In carcinomas, metastatic competence is dependent on the aberrant activation of a latent embryonic program called the epithelial-mesenchymal transition (EMT).
“In our work, we identified p38 as a critical regulator of metastasis by regulating the stability and function of the transcription factor FOXC2 in the context of cells with mesenchymal and stem cell traits,” said Mani, lead author of the published study. “Our results link p38-FOXC2 crosstalk to the activation of multiple independent EMT programs underpinning the acquisition of stem cell properties.”
According to Mani, the findings suggest a link between FOXC2 elevation and p38 activation in metastasis-prone tumors.
“The data contributes valuable insight into the poorly understood regulation of metastasis, but also unveils a selective therapeutic vulnerability of metastases to p38 inhibitors. Collectively, this demonstrates that FOXC2, a key downstream mediator of EMT regulates stem cell traits and metastasis in a p38-dependent manner and attests to the potential utility of p38 inhibitors as anti-cancer stem cell and anti-metastatic agents.”