SCI ADV: Identifies a specific regulator that promotes breast cancer development

27-hydroxycholesterol (27-HC, 27-hydroxy) is the most abundant oxysterol that increases the risk of breast cancer progression, but researchers do not currently know the epigenetic regulation of 27-HC metabolism and the key role
it plays in breast tumorigenesis 。 Recently, a study entitled "ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells" published in the international journal Science Advances, Scientists from the University of Texas Southwestern Medical Center and other institutions have identified a pathogenic signaling pathway in breast cancer, which may provide potential new targets for the development of new therapies to treat this common breast cancer
.

The study builds on previous studies in which researchers identified a gene called ZMYND8 that may act as a regulator of breast tumor growth, in which the researchers further analyzed the key role of ZMYND8 and the level of 27-hydroxycholesterol in breast cancer, said Weibo Luo, who identified a cause of breast cancer, the leading cause of cancer-related deaths in women worldwide.
The new findings represent another important step
toward developing new and effective therapies and determining a patient's breast cancer risk as early as possible.

Breast cancer begins with a population of cells called breast cancer stem cells, which have superior self-replicating abilities, and these "bad seeds" drive tumor growth, but how it occurs is not clear to researchers
.
After identifying ZMYND8 as a regulator of breast cancer growth, researcher Luo and others wanted to determine whether the gene plays an important role
in tumorigenesis.
Using mouse models of knockout of ZMYND8 and complementary cell culture experiments, the researchers found that ZMYND8 promotes the maintenance and self-renewal of breast cancer stem cells and can stimulate these cells to transform into tumor cells, leading to breast tumors
.

Identification of a special regulator that promotes breast cancer development
.

Image source: Science Advances (2022).
DOI:10.
1126/sciadv.
abn5295

The researchers pointed out that the activity of ZMYND8 leads to an increase in the production of 27-hydroxycholesterol (the main product of cholesterol oxidation in the human body), and also blocks the breakdown of 27-hydroxycholesterol; Cholesterol can help control cell survival and growth, and 27-hydroxycholesterol was previously thought to regulate estrogen receptors to promote the progression of ER-positive breast cancer, but its role in breast cancer stem cells and tumor opening has never been investigated by researchers
.

The resulting accumulation of 27-hydroxycholesterol leads to the activation of liver X receptor (LXR), which alters gene expression, and this ZMYND8-27-hydroxycholesterol-LXR axis together promotes the activity of ER-positive and triple-negative breast cancer stem cells and promotes their growth into breast tumors
。 Researcher Luo added that the study revealed that ZMYND8 and 27-hydroxycholesterol may be therapeutic targets for the development of novel therapies for breast cancer, as well as possible biomarkers that can help predict the risk of breast cancer recurrence and metastasis in patients
.
In summary, the results of this study suggest that ZMYND8 may be able to act as a special epigenetic promoter to drive the occurrence
of breast tumors through metabolic reprogramming.
(Biovalley Bioon.
com)

Original source:

MAOWU LUO,LEI BAO,YAN CHEN, et al.
 ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells, Science Advances (2022).
DOI: 10.
1126/sciadv.
abn5295