Abstract 4997: MMP14 as PTP4A3 downstream target is involved in uveal melanoma cell dissemination

Abstract

Abstract Abstract: Uveal melanoma is the most common intraocular malignancy in adults, representing 5% of all melanomas. Although at diagnosis over 95% of patients have disease limited to the eye, about 50% will develop metastases after a median period of 36 months. High expression levels of Protein Tyrosine Phosphatase 4A3 (PTP4A3), a dual phosphatase, is highly predictive of metastasis development and PTP4A3 overexpression in uveal melanoma cells increases their in vitro migration and in vivo invasiveness. The PTP4A3 mechanism of action in the tumoral process is poorly understood. We identified the metalloprotease MMP14 as an interacting partner of PTP4A3. MMP14 is more abundant at the cell membrane in PTP4A3 invasive cells compared to control cells (inactive catalytic site mutant GFP-PTP4A3(C104S) or EGFP) and inhibition of MMP14 expression decreases PTP4A3-induced cell invasiveness. The MMP14-differential cell membrane localization in presence of PTP4A3 is currently investigated by studying the trafficking of MMP14 in these cells. Citation Format: Selma Maacha. MMP14 as PTP4A3 downstream target is involved in uveal melanoma cell dissemination. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4997. doi:10.1158/1538-7445.AM2014-4997