Osteopontin and breast cancer metastasis: Possible role of genistein on the regulation of osteopontin

Background: Cancer metastasis is one of the major clinical challenges worldwide and is highly associated with patient's deaths. Therefore, targeting metastatic related proteins is the key to the development of anticancer therapy. Osteopontin (OPN) overexpression is associated with breast cancer progression and metastasis; thus, it is considered a promising biomarker. Many in vitro and in vivo studies have been reported that the use of isoflavones (particularly genistein) for the treatment of different types of cancer, including breast cancer, be promising chemopreventive agents. However, their precise mode of action in breast cancer treatment remains unclear till today. Methods: Literature survey was performed for screening out the genistein with therapeutic potentials and their mode of action using published articles available at the web databases in the public domains (like PubMed, SCI Finder, Science Direct, and Google Scholar) till June 2021. Results: In this review article, we have reviewed the development of novel anti-tumour strategies like inhibition of OPN at the transcriptional- or translational- level, development of monoclonal antibodies against OPN, and its downstream signalling pathways, etc. The inhibitory effect of the isoflavone(s) (e.g. genistein) on breast cancer proliferation, migration and invasion has also been reviewed. A newly elucidated anti-carcinogenic mode of action of the isoflavone including epigenetic modifications, topoisomerase inhibition and modulation of miRNA expression has also been discussed. Reports on the regulation of OPN expression by the isoflavone and the signalling pathways involved therein have been reviewed. Conclusion: Taken together, the isoflavone (genistein) could be used as a promising agent for cancer chemoprevention and/or treatment, though more clinical trials are needed for its validation.