Chinese Scientists Reveal the Mechanism of The Carcinogenesis of Stem Cells
Scientists at Zhejiang University found in their stem cell research that when two key proteins go “out of control” and collide, a series of changes will be triggered and turn a normal stem cell into a cancer stem cell. This discovery provided a new idea for cancer treatment.
Stem cells are regarded as “wildcard cells” due to their multiple differentiation and self-renewal abilities. As Professor Wang Yingjie introduced, “Pluripotent stem cells have a ‘privilege’ that they can differentiate into different types of body cells for the replacement and repair of various tissues. Thanks to this feature, they can be widely used in regenerative medicine.” Stem cells are like “eternal seeds” planted. With asymmetric division, in the formation of progeny differentiated cells, they can clone stem cells almost identical to the maternal stem cells to ensure the continuation of their potential of differentiation. This proliferation of stem cells is called “self-renewal”.
"However, when carcinogenesis happens with these “eternal seeds”, the problem becomes particularly serious because cancer cells become ever-expanding and difficult to remove.” This phenomenon is observable in some cancer patients receiving radiotherapy and chemotherapy. The differentiated tumor cells can be killed in these therapies, while cancer stem cells are still alive, or they may seem to be gone, but strike back again after a period of time and get intensified. Current radiotherapy and chemotherapy cannot eliminate them.
Wang’s research tried to discover the possible direct connection between transcription factor Oct4 and protein kinase Akt. The experiment Dr. Wang did after returning to Zhejiang University was to confirm in vitro biochemical experiment that Oct4 can indeed be phosphorylated by Akt. His research team made relevant tests on embryonic stem cells and embryonal carcinoma cells – the stem cells of malignant teratoma. Their experiments found the level of Oct4 phosphorylated by Akt was significantly higher in embryonal carcinoma cells than in embryonic stem cells.
"The interaction between the two proteins significantly get enhanced in embryonal carcinoma cells. Akt will add phosphate groups to Oct4 protein, thereby inhibiting its degradation by proteasome and enhancing its stability.” They found that as the assistants of Oct4, the added phosphate groups helped Oct4 be located in the nucleus, and promoted the formation of complexes with Oct4 and another stem cell transcription factor Sox2. These made it easier to start the transcription of relevant genes to maintain the self-renewal of stem cells, and thus enhanced the self-renewal capacity of embryonal carcinoma cells.
"We found an important mechanism of the carcinogenesis of stem cells. Next, we need to understand whether this mechanism is universal in cancer stem cells. If it is universal, the therapy that blocks ‘Oct4-Akt positive feedback loop system’ will bring a major breakthrough for the removal of cancer stem cells in cancer treatment.”
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