Abstract 2905: Deciphering and blocking the mechanisms of cadmium induction of TCTP in prostate cancer cells

Abstract

Abstract While cadmium is a well-known lung carcinogen, its role in prostate cancer is yet to be understood. Recently, a meta-analysis study showed that cadmium did not increase the risk of prostate cancer. It is not known whether cadmium exposure at environmentally relevant concentrations increases aggressiveness of already existing prostate cancer. Although our lab previously showed that the 75th percentile of cadmium concentration in prostate cancer was associated with biochemical recurrence, more evidence is needed to substantiate this finding. We also showed evidence that cadmium promotes prostate cancer cells migration and invasion via inducing the expression of translationally controlled tumor protein (TCTP). Furthermore, it was demonstrated that cadmium induces the phosphorylation of p38, and that the p38 inhibitor SB203580 (SB) blocks the effects of cadmium on migration and invasion. In this study, we aimed to delineate the signaling events upon cadmium treatment; whether p38 or TCTP is upstream. We addressed this via inhibition of p38 using SB203580 and by inducing TCTP degradation via dihydroartemisinin (DHA) followed by measurement of TCTP expression and phosphorylation of p38 respectively. p38 inhibition led to the increased expression of TCTP on both mRNA and protein levels. Pretreatment with DHA led to less TCTP expression and less phosphorylation of p38. We also aimed to understand the effect of cadmium on cell proliferation, survival and migration. While DHA lowered the colony count and EdU incorporation, cadmium did not alter these functions. In addition, DHA abrogated the cadmium-mediated migration of PC3-Inv prostate cancer cell line. Furthermore, we aimed to determine the effect of nanomolar cadmium concentrations on the phosphorylation of PlK1, which is well established to be upstream of TCTP. Our results demonstrated that nanomolar concentrations of cadmium resulted in increased phosphorylation of PlK1 in both PC3 and LNCaP cells. Altogether, our results suggest that environmentally relevant exposures of cadmium induce TCTP expression through several pathways, and that there is a feedback mechanism between p38 and TCTP. Citation Format: Rama Saad, Gnanasekar Munirathinam, Theresa Kucynda, Marta Ribeiro, Paul Lindholm, Andre Balla. Deciphering and blocking the mechanisms of cadmium induction of TCTP in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2905.