Protein ZEB1 promotes breast tumor resistance to radiation therapy

PUBLIC RELEASE DATE:

4-Aug-2014

Contact: Ron Gilmore rlgilmore1@mdanderson.org 713-745-1898 University of Texas M. D. Anderson Cancer Center

Twist, Snail, Slug. They may sound like words in a children's nursery rhyme, but they are actually the exotic names given to proteins that can generate cells with stem cell-like properties that have the ability to form diverse types of tissue.

One protein with the even more out-there name of ZEB1 (zinc finger E-box binding homeobox 1), is now thought to keep breast cancer cells from being successfully treated with radiation therapy, according to a study at The University of Texas MD Anderson Cancer Center in Houston.

Li Ma, Ph.D., an assistant professor of experimental radiation oncology at MD Anderson, reported in this month's issue of Nature Cell Biology that ZEB1 may actually be helping breast tumor cells repair DNA damage caused by radiation treatment by ramping up a first-line of defense known as DNA damage response pathway.

"Radiation therapy causes cell death by inducing DNA ' breaks'," said Ma. "The rationale for treating tumors with radiation without damaging normal tissues is that, compared with normal cells, tumor cells are actively dividing and often have defects in DNA damage repair machinery."

Tumor cells are thus less able to repair DNA damage. But not always. Sometimes the body produces tumor cells resistant to radiation. They are somehow able to "turn on" the DNA damage response apparatus. Until now, the question has always been how?

Ma's team has demonstrated that the wily tumor cell's ability to push the panic button at the last second can be triggered by ZEB1's penchant for launching an operation that generates cancer stem cells.

"The cancer stem cells have been shown to promote radioresistance through activation of the DNA damage response system," said Ma. "Our studies have shown that ZEB1 can induce a process known as epithelial-mesenchymal transition (EMT) which allows certain tumor to acquire cancer stem cell properties including radioresistance."

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Protein ZEB1 promotes breast tumor resistance to radiation therapy