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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 ER\u03b1 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, ER\u03b1, 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 ER\u03b1 signaling pathway, which restricted ER\u03b1 to be an uncontrolled active status. Combined with other peoples\u2019 researches that Hippo signaling maintained ER expression and ER\u2009+\u2009BC growth, we believed that there should exist a regulative feedback loop formation among ER\u03b1, 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.<\/jats:p>","DOI":"10.1038\/s41419-021-04338-8","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:29:49Z","timestamp":1635812989000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["ARSD, a novel ER\u03b1 downstream target gene, inhibits proliferation and migration of breast cancer cells via activating Hippo\/YAP pathway"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3878-3496","authenticated-orcid":false,"given":"Yun","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-2230","authenticated-orcid":false,"given":"Hongchao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-0123","authenticated-orcid":false,"given":"Yaochen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"4338_CR1","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1158\/1055-9965.EPI-16-0858","volume":"26","author":"LA Torre","year":"2017","unstructured":"Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. 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