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Secretion\u2010associated Ras\u2010related GTPase 1A (SAR1A) is a key regulator of endoplasmic reticulum (ER) homeostasis, but its role as a regulator of osteosarcoma metastasis has yet to be clarified. Bioinformatics analyses revealed <jats:italic>SAR1A<\/jats:italic> and <jats:italic>RHOA<\/jats:italic> to be upregulated in osteosarcoma patients, with the upregulation of these genes being associated with poor 5\u2010year metastasis\u2010free survival rates. In addition, the upregulation of <jats:italic>SAR1A<\/jats:italic> and <jats:italic>RHOA<\/jats:italic> in osteosarcoma was highly positively correlated. Immunohistochemical analyses additionally revealed that SAR1A levels were increased in osteosarcoma pulmonary metastases. In vitro wound healing and Transwell assays indicated that knocking down SAR1A or RHOA impaired the invasive and migratory activity of osteosarcoma cells, whereas RHOA overexpression had the opposite effect. Western blotting and immunofluorescent staining revealed the inhibition of osteosarcoma cell epithelial\u2013mesenchymal transition following SAR1A or RHOA knockdown; RHOA overexpression had the opposite effect. Following SAR1A knockdown, phalloidin staining indicated that osteosarcoma cells showed reduced lamellipodia formation. Endoplasmic reticulum stress levels and reactive oxygen species production were enhanced following the knockdown of SAR1A, as was autophagic activity, with lung metastases being reduced in vivo after such knockdown. Knocking down SAR1A suppresses osteosarcoma cell metastasis through the RhoA\/YAP, ER stress, and autophagic pathways, offering new insights into the regulation of autophagic activity in the context of osteosarcoma cell metastasis and suggesting that these pathways could be amenable to therapeutic intervention.<\/jats:p>","DOI":"10.1111\/cas.15551","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T13:53:40Z","timestamp":1662040420000},"page":"4104-4119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>SAR1A<\/scp> regulates the <scp>RhoA<\/scp>\/<scp>YAP<\/scp> and autophagy signaling pathways to influence osteosarcoma invasion and metastasis"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6965-7404","authenticated-orcid":false,"given":"Fangbiao","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of Orthopedics, 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