title: Quiescin sulfhydryl oxidase 1 promotes invasion of pancreatic tumor cells mediated by matrix metalloproteinases.
abstract: Quiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. We previously mapped a peptide in plasma from pancreatic ductal adenocarcinoma (PDA) patients back to an overexpressed QSOX1 parent protein. In addition to overexpression in pancreatic cancer cell lines, 29 of 37 patients diagnosed with PDA expressed QSOX1 protein in tumor cells, but QSOX1 was not detected in normal adjacent tissues or in a transformed, but nontumorigenic cell line. To begin to evaluate the advantage QSOX1 might provide to tumors, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in two pancreatic cancer cell lines. Growth, cell cycle, apoptosis, invasion, and matrix metalloproteinase (MMP) activity were evaluated. QSOX1 shRNA suppressed both short and long isoforms of the protein, showing a significant effect on cell growth, cell cycle, and apoptosis. However, QSOX1 shRNA dramatically inhibited the abilities of BxPC-3 and Panc-1 pancreatic tumor cells to invade through Matrigel in a modified Boyden chamber assay. Mechanistically, gelatin zymography indicated that QSOX1 plays an important role in activation of MMP-2 and MMP-9. Taken together, our results suggest that the mechanism of QSOX1-mediated tumor cell invasion is by activation of MMP-2 and MMP-9.
authors: Arizona State University, School of Life Sciences, Tempe, AZ 85287, USA.
authors: Benjamin A
authors: BA
authors: Katchman
authors: Kwasi
authors: K
authors: Antwi
authors: Galen
authors: G
authors: Hostetter
authors: Michael J
authors: MJ
authors: Demeure
authors: Aprill
authors: A
authors: Watanabe
authors: G Anton
authors: GA
authors: Decker
authors: Laurence J
authors: LJ
authors: Miller
authors: Daniel D
authors: DD
authors: Von Hoff
authors: Douglas F
authors: DF
authors: Lake
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007797:Laminin / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D004338:Drug Combinations; D007797:Laminin; D020033:Protein Isoforms; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; D003094:Collagen; D050862:Oxidoreductases Acting on Sulfur Group Donors; C117183:QSOX1 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9