Here’s a startling fact: the retinoblastoma protein —Rb, for short — is defective or missing in nearly all cancers.
Rb is called a tumor suppressor because it prevents excessive cell growth by acting as a crucial traffic stop for the cell cycle, a process that controls the timing for a cell to divide and multiply. Without a working Rb protein, that traffic barrier on cell division is effectively removed, allowing unrestricted cell growth and a path towards cancer.
The Rb gene was cloned over two decades ago and its link to cancer has been known for years. But today in Cell Stem Cell, CIRM-funded scientists at Stanford University report an unexpected finding: Rb protein also inhibits a stem cell’s pluripotency, or it’s capacity to become any type of cell in the body. Julien Sage, a senior author of the report, described this new facet to Rb in a press release:
“We were very surprised to see that retinoblastoma directly connects control of the cell cycle with pluripotency. This is a completely new idea as to how retinoblastoma functions.”
The research team uncovered Rb’s versatility in experiments using the induced pluripotent stem cell (iPS) technique in which adult cells, such as a skin, are reprogrammed to an embryonic stem cell-like state that, in turn, can be transformed into any cell type.
Creating iPS cells is notoriously slow and inefficient. However, the Stanford scientists found that cells without Rb were much easier and faster to convert to iPS than cells with normal Rb. And when Rb protein levels in the cells were boosted, it was much more difficult to make the iPS cells — suggesting that the presence of Rb was encouraging the skin cells to remain skin and to resist reprogramming into an iPS cell. As Marius Wernig, the other senior author, sums it up:
“The loss of Rb appears to directly change a cell’s identity. Without the protein, the cell is much more developmentally fluid and is easier to reprogram into an iPS cell.”
And Dr. Sage further points out that:
“The process of creating iPS cells from fully differentiated, or specialized, cells is in many ways very similar to what happens when a cell becomes cancerous.”
So now that the team has established the Rb protein’s direct link between stem cell and cancer biology, they stand at unique vantage point to gain new insights on the inner workings of both, such as better iPS methods and new cancer therapy targets.
To hear about more aspects of Marius Wernig’s research, watch his 30 second elevator pitch below: