Enzyme could be key to stopping breast cancer¡¯s spread
BY Ron Gilmore
July 12, 2016
Medically Reviewed | Last reviewed by an MD Anderson Cancer Center medical professional on July 12, 2016
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.
, 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.¡±