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ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis
- Source :
- Journal of Clinical Investigation. May, 2018, Vol. 128 Issue 5, p1937, 19 p.
- Publication Year :
- 2018
-
Abstract
- Altered epigenetic reprogramming contributes to breast cancer progression and metastasis. How the epigenetic reader mediates breast cancer progression remains poorly understood. Here, we showed that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) is induced by HIF-1 and HIF-2 in breast cancer cells and also upregulated in human breast tumors, and is correlated with poor survival of patients with breast cancer. Genetic deletion of ZMYND8 decreases breast cancer cell colony formation, migration, and invasion in vitro, and inhibits breast tumor growth and metastasis to the lungs in mice. The ZMYND8's oncogenic effect in breast cancer requires HIF-1 and HIF-2. We further showed that ZMYND8 interacts with HIF-1[alpha] and HIF-2[alpha] and enhances elongation of the global HIF-induced oncogenic genes by increasing recruitment of BRD4 and subsequent release of paused RNA polymerase II in breast cancer cells. ZMYND8 acetylation at lysines 1007 and 1034 by p300 is required for HIF activation and breast cancer progression and metastasis. These findings uncover a primary epigenetic mechanism of HIF activation and HIF-mediated breast cancer progression, and discover a possible molecular target for the diagnosis and treatment of breast cancer.<br />Introduction Metastasis is a major clinical obstacle to curative cancer therapy and is responsible for about 90% of breast cancer-related deaths in women. The development of a benign and nonmalignant [...]
- Subjects :
- Epigenetic inheritance -- Health aspects
Zinc finger proteins -- Health aspects -- Genetic aspects
Breast cancer -- Genetic aspects -- Development and progression
Cancer metastasis -- Genetic aspects -- Development and progression
Transcription factors -- Health aspects
Health care industry
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 128
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.539646007
- Full Text :
- https://doi.org/10.1172/JCI95089