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Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the <jats:italic>SRGN<\/jats:italic> gene expression and how it regulates TGF\u03b22 and the downstream signaling of TGF\u03b22 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues. We inhibited SRGN expression and protein secretion using shRNA and we observed this inhibited the invasive motility of TNBC cancer cells <jats:italic>in vitro<\/jats:italic> and metastasis of TNBC cancer cells <jats:italic>in vivo.<\/jats:italic> SRGN protein treatment increased the expression and secretion of transforming growth factor-\u03b22 (TGF\u03b22) by activating CD44\/CREB1 signaling and promoted epithelial-to-mesenchymal transition in TNBC cells. Moreover, TGF\u03b22 treatment increased the mRNA and protein expression of the <jats:italic>SRGN<\/jats:italic> gene by activating Smad3 to target the SRGN relative promoter domain in TNBC cells. Our findings demonstrate that SRGN interacts with TGF\u03b22 which regulates TNBC metastasis via the autocrine and paracrine routes. SRGN could serve as a potential target for development of agents or therapeutics for the TNBC.<\/jats:p>","DOI":"10.1038\/oncsis.2017.53","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T13:21:09Z","timestamp":1499692869000},"page":"e360-e360","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["SRGN-TGF\u03b22 regulatory loop confers invasion and metastasis in triple-negative breast cancer"],"prefix":"10.1038","volume":"6","author":[{"given":"Z","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,10]]},"reference":[{"key":"BFoncsis201753_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1146\/annurev-med-051413-024741","volume":"66","author":"D Zardavas","year":"2015","unstructured":"Zardavas D, Piccart M . 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