In a discovery that could have implications for leukemia treatment, investigators at the University of California, San Diego School of Medicine have linked a protein associated with a vital stem cell signal to cancer growth.
The protein, called Lis1, is essential to hematopoietic stem cell (HSC) function and blood formation. HSCs are stem cells in the blood that differentiate into all other blood cells.
In a study published in Nature Genetics, researchers explain that Lis1 regulates the process of asymmetric division of HSCs, making sure that these stem cells turn into more specialized cells to provide the right balance of new blood cells. In asymmetric division, stem cells split into two cells with different characteristics--one becomes a permanently specialized cell type while the other remains undifferentiated and open for further divisions.
When researchers deleted the Lis1 protein from mouse HSCs, differentiation of stem cells sped up, creating too many specialized cells and not enough undifferentiated stem cells, which eventually resulted in a bloodless mouse.
Then, when the scientists tried blocking the Lis1 signaling pathway, they found that cancer stem cells were no longer able to renew themselves and spread.
"In this sense, the effect Lis1 has on leukemic self-renewal parallels its role in normal stem cell self-renewal," said principal investigator Tannishtha Reya, a professor in the department of pharmacology, in a statement. "Our work shows that elimination of Lis1 potently inhibits cancer growth, and identifies Lis1 and other regulators of protein inheritance as a new class of molecules that could be targeted in cancer therapy."
Reya said more research is needed to determine whether inhibiting Lis1 in cancer cells would produce negative side effects in normal cells as well. She said it's possible that drugs targeting Lis1 could be more specific and less toxic than some current hemotherapy agents that target the mechanism that controls cell division.
- see the study abstract
- read the press release