Cancer STEM Cells and ZEB1

Cancer STEM Cells and ZEB1

Dr. Weeks’ Comment:  Here is yet more data that the recommendation of chemo and radiation alone is not only inadequate but dangerous – like the doctor kicking a hornet’s nest and running away leaving the patient vulnerable. Instead, focus on preventing the cancer from recruiting cancer STEM cells:  ask your oncologist to address ZEB1 and minimize cancer resistance.

 

“…some tumor cells are able to activate their DNA damage response mechanism, and it is protein ZEB1 that enhances cancer cells’ DNA damage response. According to Dr. Ma, ZEB1 acts as a “panic button” which the cancer cells “press” in order to generate cancer stem cells and resist treatment…”

“…To overcome the obstacle of radioresistant tumor cells, it is important to identify the critical causes and to develop safe and effective new methods for treatment, including the possible use of agents that target ZEB1 and which inhibit CHK1…”

 

August 11, 2014

Protein ZEB1 Culprit In Breast Tumor Radiation Therapy Resistance

By C. Rajan, contributing writer

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Researchers at the University of Texas MD Anderson Cancer Center in Houston have reported that a protein called zinc finger E-box binding homeobox 1 (ZEB1) may allow breast cancer cells to persist despite radiation treatment.

Dr. Li Ma, assistant professor of experimental radiation oncology at MD Anderson, reports that ZEB1 may actually be helping breast tumor cells repair DNA damage caused by radiation treatment by increasing the cells’ DNA damage response pathway. The results of her study are published in this month’s issue of Nature Cell Biology.

“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.”

Thus, tumor cells cannot repair DNA damage as effectively as normal cells. However, some tumor cells are able to activate their DNA damage response mechanism, and it is protein ZEB1 that enhances cancer cells’ DNA damage response. According to Dr. Ma, ZEB1 acts as a “panic button” which the cancer cells “press” in order to generate cancer stem cells and resist treatment.

“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 tumors to acquire cancer stem cell properties including radioresistance.”

Dr. Ma and her team investigated the mechanism of this action, and found that the kinase ATM stabilizes ZEB1 when there is DNA damage, allowing it to interact with the enzyme USP7 and stabilize CHK1. This process promotes homologous recombination-dependent DNA repair.

Breast cancer is the leading cause of cancer death in women, second only to lung cancer. According to the American Cancer Society, about 1 in 8 women in the U.S. develops breast cancer in her lifetime, and there are about 40,000 deaths annually due to invasive breast cancer. Radiation is the front line therapy against breast tumors, and radio-resistance can lower a patient’s chances of beating the cancer.

“Radiation therapy plays a key role in breast cancer management,” said Ma. “To overcome the obstacle of radioresistant tumor cells, it is important to identify the critical causes and to develop safe and effective new methods for treatment, including the possible use of agents that target ZEB1 and which inhibit CHK1.”

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