Protein ZMYND8 tied to suppression of prostate cancer tumor metastasis
Study reveals protein¡¯s ability to block expression of metastasis-linked genes
MD Anderson News Release July 28, 2016
Although it reads like European license plate number, a protein known as ZMYND8 has demonstrated its ability to block metastasis-linked genes in prostate cancer, according to a study at Â鶹ӳ» MD Anderson Cancer Center. The findings, resulting from cell line and mouse model studies, are published in the July 28 online issue of .
¡°These findings are important as cancer metastasis is a complicated process and is both devastating and clinically challenging,¡± said associate professor of Molecular and Cellular Oncology. ¡°For metastasis, cancer cells acquire migratory and invasive abilities and so gaining new insight into how this occurs and how to stop metastasis is crucial. We believe this study opens a window into this process.¡±
Lee¡¯s study centered on modification of proteins crucial to gene regulation, known as histones. Alterations in histone modifications, including acetylation and methylation, are frequently associated with cancer development. Lee¡¯s group looked at ZMYND8 as a histone ¡°reader¡± that could possibly impact gene expression by recognizing these histone modifications known as histone ¡°marks.¡±
¡°It has been well documented that the effects of histone acetylation and methylation on gene expression can be mediated by specific binding proteins called ¡®readers,¡¯¡± said Lee. ¡°We identified ZMYND8 as a reader for histone marks called H3K4me1 and H3K14ac, both of which are tied to metastasis-linked genes.¡±
The research group also noted that ZMYND8 cooperated with a type of histone mark ¡°eraser¡± called JARID1D to suppress metastasis-linked genes.
¡°These findings are of special interest in light of our earlier study that JARID1D levels are lower in metastasized prostate tumors than in normal prostate and primary prostate tumors,¡± said Lee. ¡°This study revealed a previously unknown metastasis-suppressive mechanism in which ZMYND8 counteracts the expression of metastasis-linked genes by reading dual histone marks H3K4me1 and H3K14ac and cooperating with JARID1D.¡±
MD Anderson members of the study team included Na Li, Ph.D., Tsai-Yu Chen, Shilpa Dhar, Ph.D. and Pu-Yeh Kan, Ph.D., all of Molecular and Cellular Oncology; and Hong Wen, Ph.D. and Xiaobing Shi, Ph.D., Epigenetics and Molecular Carcinogenesis.
Other participating institutions included Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing; The Methodist Hospital Research Institute, Houston; Weill Cornell Medical College, New York City; Children¡¯s Hospital, Fudan University, Shanghai; Bloomberg School of Public Health, The Johns Hopkins University, Baltimore; the University of Miami School of Medicine, Miami; Baylor College of Medicine, Houston; Â鶹ӳ» Graduate School of Biomedical Science, Houston; and West China Hospital, Sichuan University, Chengdu, China.
The study was funded by the National Institutes of Health (CA157919, GM095659, ES025761, HG007538, GM078455 and GM105754); the Cancer Prevention and Research Institute of Texas (RP110183, RP110471 and RP140323); the Ministry of Science and Technology of China (2016FA05000700); the Tsinghua University Initiative Scientific Research Program; The Robert A. Welch Foundation (G1719); the National Natural Science Foundation of China (31400633); and the China Postdoctoral Science Foundation (2014T70069).