Cancer. That one word strikes fear into the hearts of Americans. Our own bodies grow uncontrollably, destroying us. People everywhere have been affected by it, whether the tumors feed off of them or their loved ones. Cancer can develop from environmental sources or genetically. Whatever the cause, malignant cells have the same characteristic: they divide and grow unrestrained. One pathway plays a key role in the development. This is the MAPK pathway, specifically starting with the protein Ras, leading to Erk. In addition to cancer, the Ras/MAPK and other MAPK pathways are also associated with Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis (Lou Gehrig’s disease).
Ras/MAPK Pathway in Brief
Ras is a protein that is activated by signals such as growth factors. Once activated, it can activate (which usually means phosphorylate) other proteins. For this blog post, I will focus on Ras activating Raf. Raf then activates MEK which then activates ERK. This protein will then activate several transcription factors (TF), which are molecules that encourage the turning of DNA into RNA (which can then be used to make proteins!). The majority of the TFs that ERK activates are those that encourage cellular division, growth, and migration. They also play a role in regulating cell death. With its signalling effects, the Ras/MAPK pathway plays a significant role in the development of cancerous tumors.
Role of Ras and Raf in Cancer
The genes that Ras comes from is actually a family of genes. The family includes H-Ras, K-Ras, and N-Ras. K-Ras has been found to be mutated in many types of human cancers. About 50% of colon cancer case displayed a mutation in K-Ras. Mutations in the protein right after Ras, Raf, are also present in cancer. B-Raf mutations are responsible for about 66% of melanomas, which are cancers in the skin. One of the most common mutations results in B-Raf being activated constantly. It then continuously activates the MEK. MEK’s action continues, which means MEK, ERK, and the TFs are activated as well, resulting in cellular growth that cannot be turned off.
Kind of scary, but there’s hope!
Malignant tumors exhibit uncontrolled cell growth and migration that results from genetic mutations. These mutations may have been inherited or caused by the environment. There are other oncogenes (genes that cause cancer) that are important in the development of cancer such as Rb and Myc. As we learn more about the mechanisms of cancer, we will be able to develop treatments to prevent unrestrained cell growth. A previous blog post discussed different treatment options that take advantage of our current knowledge.
MAPK: A Mechanism of Cancer
