Evidence is mounting that rogue stem cells brandishing epigenetic marks (changes in gene regulation that occur without a change in DNA sequence) are at the heart of some, if not all, cancers, says Maarten van Lohuizen, of the Netherlands Cancer Institute. He recently told a conference that his team in the Netherlands has uncovered a key protein that could stop these stem cells from becoming malignant. “This is a hot topic in the cancer field,” he explained. “To be successful in cancer therapy you need to target these stem cells: they are intrinsically resistant to chemotherapy.”
His findings suggest that polycomb proteins – powerful epigenetic regulators that normally silence genes without altering the cell’s DNA – are a key player in cancer development. Compounds that regulate these proteins could result in novel anticancer drugs that shrink malignant tissue, and prevent cancer recurrence.
Van Lohuizen found that stem cells in cancerous tissues are locked in an immature state in which they carry on multiplying instead of maturing into specific tissues. “Some resistant cancer cells don’t listen to the ‘stop’ signal any more,” he explained. That stop signal is delivered by the polycomb proteins, believes Van Lohuizen, which can silence several genes at once by affecting the way the DNA is compacted into chromatin fibers, without altering the DNA sequence.
Normally, polycomb proteins repress genes during development, or when stem cells are needed for tissue maintenance. But an aberrant polycomb spells trouble. In mice where polycomb proteins have been genetically disabled, van Lohuizen has seen that the cells become invasive and trigger cancerous growth. “This may be why gliomas are such lethal tumors, because these stem cells become highly migratory,” van Lohuizen points out. The Dutch researcher is optimistic that therapeutic agents that target these budding cancer stem cells can be found. “We have to be very careful because [these compounds] will also regulate normal stem cell behavior. It is a fine balance,” he warned.