Cellular recycling under attack

Study reveals how top cancer-causing gene inactivates key protein

By Russell Rian

Cancer researchers at UT Southwestern Medical Center have identified how a top cancer-causing gene in humans attacks a cell’s natural recycling process and thereby encourages cancer growth to flourish.

Dr. Beth Levine and Dr. Richard Wang
Dr. Beth Levine and Dr. Richard Wang

UTSW researchers studied the gene Akt, which normally tells cells to grow. To make certain that cells do not grow too quickly, another gene (beclin 1) that is involved in cell-recycling processes called autophagy, acts as a brake to Akt.  In many different types of cancers, Akt is abnormally activated. The scientists found that the excess Akt inactivates beclin 1 in the cancer cells and thus removes the brakes, allowing unregulated growth. Their investigation is described in a paper published Nov. 16 in Science.

“This work provides important insights into one of the ways that abnormal activation of Akt – and potentially other related cancer-causing genes – may function to cause cancer,” said Dr. Beth Levine, Director of the Center for Autophagy Research at UT Southwestern and senior author of the study.

Cancer-fighting researchers such as Dr. Levine, Professor of Internal Medicine and Microbiology, and a Howard Hughes Medical Institute (HHMI) investigator at UTSW, are trying to better understand how autophagy works so they can eventually learn how to control the process. Doing so might aid in getting rid of unwanted cells such as cancer cells and encourage healthy cells to thrive.

Understanding how genes such as Akt regulate natural cellular recycling is important because errors in these processes are implicated in a variety of diseases, said lead author Dr. Richard Wang, Assistant Professor of Dermatology and a member of the Center for Autophagy Research.

“Our study is important because it demonstrates that one of the most commonly activated pathways in cancer functions in part by inhibiting autophagy,” Dr. Wang said. “Our goal now is to determine whether the induction of autophagy could be used to prevent or slow the development of cancer in patients.”

Beclin 1 is one of the first known proteins in mammals found to be essential for autophagy, a finding made by Dr. Levine’s laboratory. Her research has since demonstrated that defects in the beclin 1 gene may contribute to cancer, aging, neurodegenerative diseases such as Alzheimer’s, and infectious diseases. Conversely, beclin 1 activity and the autophagy pathway appear to be important for protection against breast, lung, and ovarian cancers, as well as for fighting off viral and bacterial infections, and for protecting individuals from neurodegenerative diseases and aging.

Other UTSW researchers involved in the latest study were Dr. Michael White, Professor of Cell Biology; Dr. Yongjie Wei, Assistant Professor of Internal Medicine; Dr. Guanghua Xiao, Assistant Professor of Clinical Sciences; Zhenyi An, a research assistant in Internal Medicine; and Zhongju Zou, a research specialist with the HHMI.

The research was supported by grants from the National Institutes of Health, the National Cancer Institute, and the German Research Foundation, along with a Dermatology Foundation award.

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Dr. Levine holds the Charles Cameron Sprague Distinguished Chair in Biomedical Science.

Dr. White holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D., and the Grant A. Dove Chair for Research in Oncology.

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