Mariana Concentino Menezes Brum

Osteopontin-c gene expression and subcellular localization in ovarian cancer cells: Implications for prognosis and therapeutic responses

Background Osteopontin is a glycophosphoprotein aberrantly expressed in several tumor types, which exhibits several isoforms generated by post-translational and post-transcriptional mechanisms, including alternative splicing. Among total osteopontin (tOPN), the osteopontin-c (OPN-c) splice variant has been the most explored with an oncogenic role described for a range of tumor types. Especially in ovarian cancer (OC) cells, OPN-c is found overexpressed, presenting both diagnostic and prognostic implications. Objective In this review article, we aim to outline OPN-c roles in cancer, particularly in OC, in which it has been reported as a diagnostic biomarker. Methods We used PubMed search, and experimental procedures were summarized at the Figure legends. Results We identified cytoplasmic, perinuclear, and nuclear OPN-c in OC cells that overexpress this OPN splice variant. Moreover, we report that OPN-c splicing isoform is found highly expressed in endometrioid OC patients’ samples, compared to non-neoplastic ovarian tissues. Also, OPN-c expression levels have been associated with worse overall survival and worse progression-free survival in patients with both endometrioid and serous OC. Furthermore, OPN-c may be involved in a wide range of tumor features evoked by signaling pathways, such as AKT, ERK, and FAK. Conclusions Therefore, a better comprehension of OPN-c roles in OC can further contribute to its application as a biomarker as well as a target for putative treatment strategies, especially those aiming to sensitize tumor cells to chemotherapeutic agents currently used in the OC treatment.