Dec. 20, 2012 ? The protein kinase Akt is a pivotal regulator of dungeon growth, proliferation, metabolism, survival, and death. New work on Akt’s purpose in cancer branch dungeon biology from a lab of comparison author Honglin Zhou, MD, PhD and Weihua Li, co-first author, both from a Center for Resuscitation Sciences, Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, and Xiaowei Xu, Department of Pathology and Laboratory Medicine, appears in Molecular Cell.
The commentary were also highlighted in Nature and Science reviews.
This new investigate shows that Akt might be a pivotal as to because cancer branch cells are so tough for a physique to get absolved of. It has been documented that visit hyperactivation of Akt kinases occurs in many forms of tellurian plain tumors and blood malignancies. Prior to this work, Akt was also shown to play a pivotal purpose in a predestine of other forms of branch cells, yet those mobile mechanisms are still unclear.
“When we came to Penn in 2009, my lab initial found that Akt regulates a activity of a protein Oct4,” explains Zhou. Oct4 is one of a 4 transcriptional factors used to beget prompted pluripotent branch cells, or iPS cells. In 2006, Kyoto University researcher and Nobel Prize leader Shinya Yamanaka voiced 4 proteins — Oct 4 was one of a — in rodent somatic cells to rewind their genetic clocks, converting them into embryonic-like iPS cells.
The biochemical experiments summarized in a Molecular Cell paper reliable that Oct4 interacts directly with Akt and a adding of phosphate molecules to Oct4 by Akt regulates a stability, where it localizes in a cell, and a outcome on gene expression. Akt phosphorylating Oct4 has a outcome of creation Oct4 quit into a nucleus, where it interacts with other transcription factors and regulates aim genes transcription.
The commentary were serve extended into embryonal carcinoma cells, that are subsequent from teratocarcinomas and mostly deliberate a virulent counterparts to rudimentary branch cells (ESCs). The group showed that embryonal carcinoma cells with deregulated Akt activation and some-more phosphorylated Oct4 are some-more resistant to dungeon genocide signals such as ultraviolet irradiation and high glucose treatment.
Since Akt activation is mostly deregulated in cancer and Oct4 countenance is upregulated in cancer branch cells of several forms of cancer, a researchers are study either a Akt/Oct4 pathway plays identical roles in other forms of cancer branch cells in serve to embryonal carcinoma cells. If true, Akt inhibitor might be grown as a new drug for murdering cancer branch cells in cancer therapy.
The Molecular Cell work was been finished in partnership with Binghui Shen and Yingjie Wang from Zejiang University in China.
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Journal References:
- Yuanji Lin, Ying Yang, Weihua Li, Qi Chen, Jie Li, Xiao Pan, Lina Zhou, Changwei Liu, Chunsong Chen, Jianqin He, Hongcui Cao, Hangping Yao, Li Zheng, Xiaowei Xu, Zongping Xia, Jiangtao Ren, Lei Xiao, Lanjuan Li, Binghui Shen, Honglin Zhou, Ying-Jie Wang. Reciprocal Regulation of Akt and Oct4 Promotes a Self-Renewal and Survival of Embryonal Carcinoma Cells. Molecular Cell, 2012; 48 (4): 627 DOI: 10.1016/j.molcel.2012.08.030
- Felix Cheung. Stem cells: Caught in a act. Nature China, 2012; DOI: 10.1038/nchina.2012.74
- E. Andrianantoandro. Oct4 Connects Akt to Cancerous Stem Cells. Science Signaling, 2012; 5 (253): ec310 DOI: 10.1126/scisignal.2003837
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Source: Health Medicine Network