PO-109 Integral membrane protein 2A expression leads to enhanced anti-cancer effects and chemosensitivity in epithelial ovarian cancer

Abstract

IntroductionIn recent years, the molecular mechanisms involved in the development of ovary tumours have been studied, although little is known about the high resistance of these tumours to conventional therapies. We found that the expression of myosin phosphatase-targeting subunit 1 (MYPT1), which has been related to cancer progression, in tumour ovary samples versus normal tissues was reduced, as was also the overall survival of ovary tumour patients. MYPT1 is a known regulator of protein phosphatase 1 (PP1C), which is known to play critical roles controlling the phosphorylation states of diverse substrates in different locations and various steps of cell division.Material and methodsTo characterise the implication of MYPT1 in ovary cancer, we generated two MYPT1 knock-down ovary cancer cell lines from SKOV3 and OVCAR8 commercial cell lines and checked MYPT1 protein and mRNA levels. In additiion, we analysed tumorigenesis using different in vitro approaches: growth curves, colony formation assays, percentage of holoclones and capacity to generate tumorspheres. We also analysed several stem cell markers by FACS and RT-qPCR, as well as resistance to treatment with platin drugs in vitro (IC50) and in vivo using xenografts.Results and discussionsThe study of tumorigenesis in SKOV3 and OVCAR8 ovary tumour cell lines demonstrates that down-regulation of MYPT increases resistance to platin drugs treatment both in vivo and in vitro. Moreover, MYPT down-regulation increases tumour growth in vitro and in vivo, the ability to generate tumorspheres, and the percentage of holoclones. In addition, MYPT depletion increases several stem cell features in ovary cells lines.ConclusionAltogether, our data demonstrates that down-regulation of MYPT1 increases the resistance to platin drugs therapies, possibly because it is responsible for the increase in tumorigenesis and de-differentiation of ovarian tumour to a stem-cell phenotype.