Sci Adv: Identification of a specific regulator that promotes breast cancer

Source: Bio Valley Original 2022-11-16 09:31

Scientists from the University of Texas Southwestern Medical Center and other institutions have identified a pathogenic signaling pathway in breast cancer that may provide potential new insights into the development of new treatments for this common breast cancer. target.

27-Hydroxycholesterol(27-HC, 27-Hydroxycholesterol) is increasedbreast cancerOxysterol, the most abundant risk for progression, however, remains unclear about the epigenetic regulation of 27-HC metabolism and its critical role in breast tumorigenesis.Recently, an article published in the international journalScience AdvancesIn the research report entitled “ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells”,Scientists from the University of Texas Southwestern Medical Center and other institutions have identified a pathogenic signaling pathway in breast cancer that may provide potential new insights into the development of new treatments for this common breast cancer. target.

This study is based on previous research results. In previous studies, researchers identified a gene called ZMYND8 that may act as a regulator of breast tumor growth. In this study, researchers further analyzed the role of ZMYND8 in the development of breast cancer. key roles and levels of 27-hydroxycholesterol, said researcher Weibo Luo. Researchers have taken another important step toward developing new and effective therapies and identifying patients’ breast cancer risk as early as possible.

breast cancerstem cellA type of cell population with a superior ability to replicate itself, these “bad seeds” can drive tumor growth, but how this happens is currently unclear to researchers. After identifying ZMYND8 as a regulator of breast cancer growth, researchers Luo et al. wanted to determine whether the gene played an important role in tumorigenesis. Using ZMYND8-knockout mouse models and complementary cell culture experiments, the researchers found that ZMYND8 promotes the maintenance and self-renewal of breast cancer stem cells and stimulates the transformation of these cells into tumor cells, leading to breast tumor growth. occur.

A specific regulator that promotes breast cancer development is identified.

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 at the same time blocks the breakdown of 27-hydroxycholesterol; cholesterol helps control cell survival and growth, and 27 -Hydroxycholesterol was previously thought to regulate estrogen receptors to promote the progression of ER-positive breast cancers, but its role in breast cancer stem cells and tumor initiation had never been investigated.

The resulting accumulation of 27-hydroxycholesterol leads to activation of liver X receptor (LXR, liver X receptor), which changes gene expression, and this ZMYND8-27-hydroxycholesterol-LXR axis jointly promotes ER activity of positive and triple-negative breast cancer stem cells and drives their growth into breast tumors. Researcher Luo added that this study reveals that ZMYND8 and 27-hydroxycholesterol may serve as therapeutic targets for the development of new treatments 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 act as a special epigenetic promoter to drive breast tumorigenesis through metabolic reprogramming.bio valleyBioon.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

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