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Disruption of SUMO dynamics prompts various pathophysiological conditions, including cancer. The burden of deSUMOylating the large SUMO-proteome rests on 6 full-length mammalian SUMO-proteases or SENP. While multiple SENP isoforms exist, the function of these isoforms remains undefined. We now delineate the biological role of a novel SENP7 isoform SENP7S in mammary epithelial cells. SENP7S is the predominant SENP transcript in human mammary epithelia but is significantly reduced in precancerous ductal carcinoma <jats:italic>in situ<\/jats:italic> and all breast cancer subtypes. Like other SENP family members, SENP7S has SUMO isopeptidase activity but unlike full-length SENP7L, SENP7S is localized in the cytosol. <jats:italic>In vivo,<\/jats:italic> SUMOylated \u03b2-catenin and Axin1 are both SENP7S-substrates. With knockdown of SENP7S in mammary epithelial cells, Axin1-\u03b2-catenin interaction is lost and \u03b2-catenin escapes ubiquitylation-dependent proteasomal degradation. SUMOylated \u03b2-catenin accumulates at the chromatin and activates multiple oncogenes. Hence, non-tumorigenic MCF10-2A cells with reduced SENP7S exhibit greater cell proliferation and anchorage-dependent growth. SENP7S depletion directly potentiates tumorigenic properties of MCF10-2A cells with induction of anchorage-independent growth and self-renewal in 3D-spheroid conditions. Collectively, the results identify SENP7S as a novel mediator of \u03b2-catenin signaling and normal mammary epithelial cell physiology.<\/jats:p>","DOI":"10.1038\/srep46477","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T09:14:50Z","timestamp":1492766090000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel SUMO-Protease SENP7S Regulates \u03b2-catenin Signaling and Mammary Epithelial Cell Transformation"],"prefix":"10.1038","volume":"7","author":[{"given":"Samaneh","family":"Karami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Ming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa","family":"Bahnassy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hariprasad","family":"Thangavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram","family":"Quttina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasneem","family":"Bawa-Khalfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"key":"BFsrep46477_CR1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1007\/978-1-4419-6676-6_14","volume":"54","author":"T Bawa-Khalfe","year":"2010","unstructured":"Bawa-Khalfe, T. & Yeh, E. 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