Scimitar Equity Blog

Research from Rockefeller University shows that having too many stem cells or stem cells that live for too long, can increase the odds of developing cancer.

• By identifying a mechanism that regulates programmed cell death in precursor cells for blood or hematopoietic stem cells, the work is the first to connect the death of such cells to a later susceptibility to tumors in mice;
• It also provides evidence of the potentially carcinogenic downside to stem cell treatments, and suggests that nature has sought to balance stem cells’ regenerative power against their potentially lethal potency.

 To study the role of ARTS, the experimenters bred a line of mice genetically engineered to lack the Sept4 gene.

• Newborn ARTS deprived mice had about twice as many hematopoietic stem cells as their normal, ARTS-endowed peers and those stem cells were extraordinary in their ability to survive experimentally induced mutations;
• The increase in the number of hematopoietic progenitor and stem cells in Sept4-deficient mice brings with it the possibility of accelerating the accumulation of mutations in stem cells;
• They have more stem cells with enhanced resistance to apoptosis. In the end, that leads to more cells accumulating mutations that cannot be eliminated;
• The ARTS-deprived mice developed spontaneous tumors at about twice the rate of their controls;
• Stang made a connection between apoptosis, stem cells and cancer that has not been made in this way before: this pathway is critically important in stem cell death and in reducing tumor risk;
• The work supports the idea that the stem cell is the seed of the tumor and that the transition from a normal stem cell to a cancer stem cell involves increased resistance to apoptosis;
• ARTS interfere with molecules called inhibitor of apoptosis proteins (IAPs), which prevent cells from killing themselves;
• By inhibiting these inhibitors, under the right circumstances ARTS helps to take the brakes off the process of apoptosis, permitting the cell to die on schedule;
• Pharmaceutical companies are working to develop small molecule IAP antagonists, but this research is the first to show that inactivating a natural IAP antagonist actually causes tumors to grow;
• It also suggests that the premature silencing of the Sept4/ARTS pathway at the stem cell level may herald cancer to come.

The identification of the ARTS gene and its role in cancer cell death provides a potential target for new therapeutic approaches. (HWM and ScienceDaily)