PO-103 Regulation of prostate cancer cell growth and signalling by exercise

Abstract

Introduction Prostate cancer is the most common male cancer. Epidemiological research have shown that physical activity can reduce the mortality of prostate cancer, and we have previously shown that endurance training can increase PSA doubling time, as a surrogate of reduced cancer progression, in prostate cancer patients in active surveillance.The molecular basis of prostate cancer is not fully understood, but dysregulation of the androgen receptor (AR) is a key factor. Upstream of AR are traditional cancer-related factors including b-catenin, which is a core component of the Wnt pathway, and YAP, one of the main downstream effectors of the Hippo pathway. Recent research has shown that YAP/ TAZ is a central component of the b-catenin destruction complex thereby demonstrating a crosslink between the two pathways. Moreover, we have recently demonstrated that exerciseconditioned serum can activate Hippo signalling in breast cancer, thereby suppressing cancer cell viability. Material and methods We utilise the human prostate cancer cell lines (LNCaP and PC3) for the exercise-conditioned serum incubation experiments, using exercise-conditioned serum obtained from young healthy men who have completed 2 hours of biking. In these incubations, we have observed that post-exercise serum can reduce the viability of both LNCaP and PC3 cells with up to 10%. Results and discussions For this project we hypothesise that physical activity, due to exercise-induced catecholamines, activate the Hippo pathway, thereby restricting YAP/TAZ to the cytoplasm and keeping YAP/TAZ in the b-catenin destruction complex preventing gene transcription. This crosstalk between the Hippo-and Wnt pathway provide us with a mechanistic explanation for the inhibitory effect of physical activity on prostate cancer cell growth. Conclusion Physical activity may constitute a potential option for controlling and inhibiting prostate cancer cell growth, and the aim of this study is thus to get a more thoroughly understanding of how physical activity inhibits prostate cancer cell growth.