{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:24:59Z","timestamp":1789457099706,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","issue":"11","license":[{"start":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T00:00:00Z","timestamp":1423785600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>\n                    The molecular mechanisms of ovarian cancer cell invasion under hypoxia remain unclear. Here we employed a 3D collagen model and chick chorioallantoic membrane (CAM) invasion assay to explore the influence of hypoxia on ovarian cancer cell invasion. Hypoxia (both 1% O\n                    <jats:sub>2<\/jats:sub>\n                    and CoCl\n                    <jats:sub>2<\/jats:sub>\n                    150 and 250\u2009\u00b5M) induced HO-8910PM ovarian cancer cell invasion in 3D collagen and collagenolysis determined by hydroxyproline. Pretreatment with a hypoxia inducible factor-1\u03b1 inhibitor, YC-1, or MMP inhibitor, GM6001, significantly inhibited 3D collagen invasion and degradation and cell proliferation. Hypoxia stimulated both mRNA and protein expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP) and promoted MT1-MMP translocation to the cell surface in an YC-1 sensitive manner. MT1-siRNA transfection inhibited hypoxia-induced invasion, proliferation, and collagen degradation of cells in 3D collagen. Hypoxia stimulated Snail mRNA and protein expression as well as translocation to nucleus in an YC-1 sensitive manner. Overexpression of Snail with a recombinant plasmid in HO-8910PM cells resulted in an enhanced invasion in 3D collagen. Transfection with Snail-specific siRNA significantly decreased MT1-MMP expression and 3D collagen invasion. Hypoxia-treated cells significantly broke the upper CAM surface of 11-day-old chick embryos and infiltrated interstitial tissue, completely blocked in the presence of YC-1 or GM6001, or after MT1-MMP siRNA or Snail siRNA transfection. Together, these data suggest that hypoxia promotes HO-8910PM ovarian cancer cell traffic through 3D matrix via Snail-mediated MT1-MMP upregulation, a possible molecular mechanism of ovarian cancer cell invasion under hypoxia.\n                  <\/jats:p>","DOI":"10.1177\/1535370215570205","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T23:25:02Z","timestamp":1423869902000},"page":"1434-1445","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Hypoxia promotes HO-8910PM ovarian cancer cell invasion via Snail-mediated MT1-MMP upregulation"],"prefix":"10.3389","volume":"240","author":[{"given":"Lijun","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University,Harbin, Heilongjiang 150081, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University,Harbin, Heilongjiang 150081, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University,Harbin, Heilongjiang 150081, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Li","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlian","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University,Harbin, Heilongjiang 150081, P. R. 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