Protein kinase Akt identified as arbiter of cancer stem cell fate, paper reports

December 20, 2012, University of Pennsylvania School of Medicine
Signaling via the Akt serine/threonine protein kinase plays critical roles in the self-renewal of embryonic stem cells and their malignant counterpart, embryonal carcinoma cells. Credit: Honglin Zhou, Perelman School of Medicine, University of Pennsylvania; Molecular Cell

(Medical Xpress)—The protein kinase Akt is a key regulator of cell growth, proliferation, metabolism, survival, and death. New work on Akt's role in cancer stem cell biology from the lab of senior author Honglin Zhou, MD, PhD and Weihua Li, co-first author, both from the 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 findings were also highlighted in Nature and Science reviews.

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 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 , or iPS cells. In 2006, Kyoto University researcher and Shinya Yamanaka expressed four proteins – Oct 4 was one of the - in mouse 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 and regulates 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.

Explore further: Researchers find more clues to causes of breast cancer

More information: Paper: download.cell.com/molecular-ce … 1097276512007745.pdf
stke.sciencemag.org/cgi/conten … ec310?printview=true
www.nature.com/nchina/2012/121 … /nchina.2012.74.html

Related Stories

Researchers find more clues to causes of breast cancer

October 27, 2011
Publishing in the current issue of The Journal of Biological Chemistry (Vol. 286, No 43), researchers at Moffitt Cancer Center in Tampa, Fla., have discovered additional mechanisms of "Akt" activation and suggest a component ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.