Hutchinson Center study sheds new light on cancer cells
By Ignacio Lobos, Hutchinson Center External Communications Editor
Mitochondria are the power plants of cells, providing needed energy to function properly. So, it would seem reasonable to assume that in cancer cells, these power plants would be out of control, spinning into countless mutations to feed the growth of malignant cells.
But the opposite is true, according to a new finding that challenges previously held beliefs about the role of mutations in cancer development. When Hutchinson Center geneticist Jason Bielas looked at colon cancer cells, he discovered that the number of new mutations in the mitochondria of malignant cells were significantly lower than in normal cells. His findings were published in the June 7 issue of PLoS Genetics.
There’s plenty to cheer in this finding. It resets what researchers know about the role of mutations in cancer development and it gives them new avenues of exploration as they seek cures.
“This work started with the idea that there would be a huge mutation burden in the mitochondrial DNA, but our findings were completely opposite of what we had expected,” said Bielas, who was attempting to determine whether mitochondrial DNA could be used as a cancer biomarker. Instead, it could become a new drug target.
“Hopefully our discovery will open up new avenues for treatment, early detection and monitoring treatment response of colon cancer and other malignancies,” he said.
Mutations are changes in the genetic sequence of a cell’s genome and can occur as a result of environmental exposure to viruses, radiation and certain chemicals, or due to spontaneous errors during cell division or DNA replication.
Mitochondria, which are primarily responsible for cells’ energy production, are semi-autonomous; similar to the nucleus, they have their own set of DNA, which encodes genes critical for the functioning of the cell.
Now that we know there’s different rates of mutation going on in a cancerous cell, it may be possible to pursue a couple of different approaches to destroy it and prevent cancer from spreading.
It may be possible, with new drugs, to increase mitochondrial mutation rates so they serve as a barrier to cancer development. It may also be possible to develop “drugs that focus directly on increasing mitochondrial DNA damage and mutation,” which could lead to accelerated aging and tumor-cell death, Bielas said. “This is a whole new hypothesis.”
There’s another potential area of discovery, and it involves oxygen—or the lack of it.
The way mitochondria maintain genetic stability in the face of cancer, Bielas suggests, may be because unlike normal cells, cancer cells do not need oxygen to survive. In fact, cancer cells decrease the process by which they get energy from the mitochondria and rely instead on a process called glycolysis, which is a form of energy production in the absence of oxygen.
“We believe less damage occurs to mitochondrial DNA of cancer cells because they no longer need oxygen,” Bielas said. “If we could program a cancer cell to once again need oxygen, we expect it would die—with minimal side effects.”
Bielas and colleagues are now testing this theory in the laboratory, seeing whether cancer cells that are reprogrammed to utilize oxygen and/or are targeted for mitochondrial DNA damage respond better to certain therapeutic agents.