Protein Kinase Akt Identified As Arbiter Of Cancer Stem Cell Fate, According To Penn Study
This new research shows that Akt may be the key as to why cancer stem cells are so hard for the body to get rid of. It has been documented that frequent hyperactivation of Akt kinases occurs in many types of human solid tumors and blood malignancies. Prior to this work, Akt was also shown to play a pivotal role in the fate of other types of stem cells, though those cellular mechanisms are still unclear.
"When I came to Penn in 2009, my lab first found that Akt regulates the activity of the protein Oct4," explains Zhou. Oct4 is one of the four transcriptional factors used to generate induced pluripotent stem cells, or iPS cells. In 2006, Kyoto University researcher and Nobel Prize winner Shinya Yamanaka expressed four proteins - Oct 4 was one of the - in mouse somatic cells to rewind their genetic clocks, converting them into embryonic-like iPS cells.
The biochemical experiments outlined in the Molecular Cell paper confirmed that Oct4 interacts directly with Akt and the adding of phosphate molecules to Oct4 by Akt regulates its stability, where it localizes in a cell, and its effect on gene expression. Akt phosphorylating Oct4 has the effect of making Oct4 migrate into the nucleus, where it interacts with other transcription factors and regulates target genes transcription.
The findings were further extended into embryonal carcinoma cells, which are derived from teratocarcinomas and often considered the malignant counterparts to embryonic stem cells (ESCs). The team showed that embryonal carcinoma cells with deregulated Akt activation and more phosphorylated Oct4 are more resistant to cell death signals such as ultraviolet irradiation and high glucose treatment.
Since Akt activation is often deregulated in cancer and Oct4 expression is upregulated in cancer stem cells of various types of cancer, the researchers are studying whether the Akt/Oct4 pathway plays similar roles in other types of cancer stem cells in addition to embryonal carcinoma cells. If true, Akt inhibitor may be developed as a new drug for killing cancer stem cells in cancer therapy.
The Molecular Cell work was done in collaboration with Binghui Shen and Yingjie Wang from Zejiang University in China.
University of Pennsylvania School of Medicine
Source: EurekAlert!, the online, global news service operated by AAAS, the science society
Please use one of the following formats to cite this article in your essay, paper or report:
University of Pennsylvania School of Medicine. "Protein Kinase Akt Identified As Arbiter Of Cancer Stem Cell Fate, According To Penn Study." Medical News Today. MediLexicon, Intl., 2 Jan. 2013. Web.
30 Sep. 2016. <http://www.medicalnewstoday.com/releases/254384.php>
University of Pennsylvania School of Medicine. (2013, January 2). "Protein Kinase Akt Identified As Arbiter Of Cancer Stem Cell Fate, According To Penn Study." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
Contact our news editors
For any corrections of factual information, or to contact our editorial team, please see our contact page.
Copyright Medical News Today: Excluding email/sharing services explicitly offered on this website, material published on Medical News Today may not be reproduced, or distributed without the prior written permission of Medilexicon International Ltd. Please contact us for further details.