Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

作者：Wilson Andrew J; Fadare Oluwole; Beeghly Fadiel Alicia; Son Deok Soo; Liu Qi; Zhao Shilin; Saskowski Jeanette; Uddin Md Jashim; Daniel Cristina; Crews Brenda; Lehmann Brian D; Pietenpol Jennifer A; Crispens Marta A; Marnett Lawrence J; Khabele Dineo^*

来源：Oncotarget, 2015, 6(25): 21353-21368.

DOI：10.18632/oncotarget.3860

• high-grade serous ovarian cancer
• cyclooxygenase-1
• cell migration/invasion
• pro-tumorigenic pathways

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.

• 出版日期2015-8-28