title: New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.
abstract: The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.
authors.affiliation: VBCRC Invasion and Metastasis Unit, St Vincent's Institute, Fitzroy, VIC, Australia. honorjoyhugo@gmail.com.
authors.forename: Honor J
authors.identifier: http://orcid.org/0000-0003-1382-5039
authors.initials: HJ
authors.lastname: Hugo
authors.affiliation: School of Surgery, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Saunders
authors.affiliation: Differentation and Transcription Laboratory, Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: R G
authors.initials: RG
authors.lastname: Ramsay
authors.affiliation: VBCRC Invasion and Metastasis Unit, St Vincent's Institute, Fitzroy, VIC, Australia.|Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland Institute of Technology, Brisbane, QLD, Australia.|Department of Surgery, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: E W
authors.initials: EW
authors.lastname: Thompson
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020598:Proto-Oncogene Proteins c-myb; D051546:Cyclooxygenase 2
keywords: Breast cancer; COX-2; Chronic inflammation; EMT; HIF1α; c-Myb