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ARSD, a novel ERα downstream target gene, inhibits proliferation and migration of breast cancer cells via activating Hippo/YAP pathway
- Source :
- Cell Death and Disease, Vol 12, Iss 11, Pp 1-14 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Advanced breast cancer (BC), especially basal like triple-negative BC (TNBC), is a highly malignant tumor without viable treatment option, highlighting the urgent need to seek novel therapeutic targets. Arylsulfatase D (ARSD), localized at Xp22.3, is a female-biased gene due to its escaping from X chromosome inactivation (XCI). Unfortunately, no systematic investigation of ARSD on BC has been reported. In this study, we observed that ARSD expression was positively related to ERα status either in BC cells or tissue specimens, which were associated with good prognosis. Furthermore, we found a set of hormone-responsive lineage-specific transcription factors, FOXA1, GATA3, ERα, directly drove high expression of ARSD through chromatin looping in luminal subtype BC cells. Opposingly, ARSD still subjected to XCI in TNBC cells mediated by Xist, CpG islands methylation, and inhibitory histone modification. Unexpectedly, we also found that ectopic ARSD overexpression could inhibit proliferation and migration of TNBC cells by activating Hippo/YAP pathway, indicating that ARSD may be a molecule brake on ERα signaling pathway, which restricted ERα to be an uncontrolled active status. Combined with other peoples’ researches that Hippo signaling maintained ER expression and ER + BC growth, we believed that there should exist a regulative feedback loop formation among ERα, ARSD, and Hippo/YAP pathway. Collectively, our findings will help filling the knowledge gap about the influence of ARSD on BC and providing evidence that ARSD may serve as a potential marker to predict prognosis and as a therapeutic target.
- Subjects :
- Cancer Research
Immunology
Breast Neoplasms
Triple Negative Breast Neoplasms
Hormone receptors
Biology
Models, Biological
Article
Histones
Cellular and Molecular Neuroscience
Cell Movement
X Chromosome Inactivation
Cell Line, Tumor
Humans
Hippo Signaling Pathway
Transcription factor
Arylsulfatases
Cell Proliferation
Chromosomes, Human, X
Binding Sites
Base Sequence
QH573-671
Estrogen Receptor alpha
GATA3
YAP-Signaling Proteins
Cell Biology
DNA Methylation
Middle Aged
Chromatin
Gene Expression Regulation, Neoplastic
Mechanisms of disease
Phenotype
Histone
Hippo signaling
Disease Progression
biology.protein
Cancer research
RNA, Long Noncoding
XIST
FOXA1
Signal transduction
Cytology
Protein Processing, Post-Translational
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....b1b5cd34542d8848f14a9521eb2c5ce4