Protein Associated with Metastatic Breast Cancer Interview with:
Yingfei Wang, Ph.D. and Weibo Luo, Ph.D.
Department of Pathology
UT Southwestern Medical Center
Dallas TX 75390 What is the background for this study?

Response: Breast cancer is the most commonly diagnosed cancer in women. Tumor metastasis is frequently found in breast cancer patients and causes more than 90% of cancer death. There is currently no cure for this deadly disease. We have known that breast tumor is not supplied with sufficient oxygen (a phenomenon known as hypoxia), which makes breast cancer cells more aggressive and may be responsible for tumor recurrence, metastasis, and therapy resistance. Hypoxia-inducible factor (HIF) is a master regulator frequently detected in the hypoxic regions and switches on many oncogenes needed for breast cancer cells to grow and spread around the body. The role of HIF in gene regulation is precisely controlled and shutting down of HIF’s activity would be a promising strategy for the treatment of metastatic breast cancer. What are the main findings?

Response: We discovered a protein called ZMYND8 that is frequently found in all molecular subtypes of breast tumors and its level is much higher in metastatic breast tumors. ZMYND8 protein predicts poor survival of patients with breast cancer. Depletion of ZMYND8 protein promotes breast cancer cell death and blocks the growth of new blood vessels in tumors leading to reduced breast cancer growth and metastasis in mice. We further identified the molecular mechanism underlying ZMYND8-mediated breast cancer progression and metastasis. We showed that ZMYND8 protein is induced by HIF in breast cancer cells. On the other hand, ZMYND8 protein increases HIF activity to activate hundreds of HIF-dependent oncogenes in breast cancer cells. ZMYND8 protein is modified with two chemical acetyl groups by the enzyme p300 and this modified ZMYND8 protein recruits another gene transcriptional regulator BRD4 protein to DNA where HIF binds, eventually leading to increased levels of HIF-controlled oncogenes to drive breast tumor malignancy. What should readers take away from your report?

Response: ZMYND8 protein may serve as a biomarker to predict breast tumor malignancy. Our study also reveals ZMYND8 as a new molecular target for the diagnosis and treatment of metastatic breast cancer. What recommendations do you have for future research as a result of this work?

Response: Further studies are needed to identify the chemicals inhibiting ZMYND8 protein as new therapeutic approaches to kill metastatic breast cancer cells, thereby reducing the incidence of metastatic spread in this very aggressive and deadly form of breast cancer.

The authors have no financial conflict. This work was supported by the Susan G. Komen®, the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society/UTSW Simmons Comprehensive Cancer Center.  


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Last Updated on April 16, 2018 by Marie Benz MD FAAD