title: Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer.
abstract: Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors.
authors.affiliation: Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
authors.affiliation: Department of Pathology, University of California San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.affiliation: Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Beeghly-Fadiel
authors.affiliation: Department of Biochemistry & Cancer Biology, Meharry Medical College, Nashville, TN, USA.
authors.forename: Deok-Soo
authors.initials: DS
authors.lastname: Son
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Vanderbilt Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Shilin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Saskowski
authors.affiliation: Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Md Jashim
authors.initials: MJ
authors.lastname: Uddin
authors.affiliation: Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Crews
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lehmann
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pietenpol
authors.affiliation: Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Crispens
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.affiliation: Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Dineo
authors.initials: D
authors.lastname: Khabele
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology*; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology*; D015398:Signal Transduction
chemical_list: D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human
keywords: cell migration/invasion; cyclooxygenase-1; high-grade serous ovarian cancer; pro-tumorigenic pathways