CDK1 is a "normal" protein; its presence drives cells through the cycle of replication. And MHC Class I molecules are "normal" as well; they present bits of proteins on the surfaces of cells for examination by the immune system. But a University of Colorado study published this week in Cancer Research shows that a population of cancer cells marked by MHC Class I molecules and high CDK1 is anything but normal. These cells may just be the long-sought cancer stem cells that often resist treatments like chemotherapy.
The goal of this study was to find out what cellular factors initiate tumor growth. To answer this question, the study used patient samples, mouse models, and publicly available genetic data to search for the genetic commonalities in cells capable of initiating melanoma, pancreatic cancer, and colon cancer.
The findings start with the MHC Class I molecule, which presents proteins to the immune system. If the proteins are not from host tissue, the immune system recognizes the cell as foreign and attacks it. For this reason, most cancer cells downregulate MHC. But this particular population of cancer cells does not. In fact, if anything, it upregulates it.
In fact, these also have high levels of CDK1. CDK1 is a master regulator of the cell cycle. With CDK1, cells progress through the cycle of replication; without CDK1, they do not. In this case, the more CDK1, the more able melanoma cells were to initiate new tumors.
"Our next question was why," says Mayumi Fujita, M.D.–Ph.D., of CU. "Why would CDK1 control not just the cell cycle but also stem-ness?"
The answer involves another protein called Sox2. Sox2 is a transcription factor that helps other stem cells keep their stem-ness. It is also a known marker of cancer stem cells, implicated in the development of more than 25 forms of the disease. This study found that CDK1 directly interacted with Sox2 to maintain the stem-ness of these cancer cells.
Moving forward, the team hopes to further define the mechanism of Sox2 regulation via CDK1 in hopes of finding essential links that might be targets for new drugs aimed, eventually, at stopping the action of Sox2.