Inhibiting ROR1 expression in Androgen-Independent Prostate Cancer Reduces Aggressive Cancer Phenotypes by modulation of AKT-GSK3ꞵ Pathway

Philadelphia, PA

Prostate cancer is a disease that has a high prevalence and mortality amongst men. The severity of the cancer is stratified by risk, which is based on the Gleason grade, prostate-specific antigen (PSA) level, and clinical staging. Unlike breast cancer which can be classified into subtypes based on molecular heterogeneity, prostate cancer has no such classification and is treated with observation, prostatectomy, or radiation if local, and non-specific chemotherapy and androgen deprivation therapy (ADT) if metastatic. It is of the utmost importance to investigate molecular targets that can specifically eradicate prostate cancer while retaining the functions of normal tissue. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a receptor that is highly expressed in embryogenesis and cancer, while being minimally expressed in normal, developed tissue. In particular, prostate cancer exhibits moderate to high levels of ROR1 expression. Previous research has been performed on ROR1 expression in various cancers and its role in promoting cancerous phenotypes. The goal of this study is to elucidate the role of ROR1 in aggressive prostate cancer in order to validate ROR1 as a potential chemotherapeutic target and as a predictor of aggressive prostate cancer. We hypothesize that knocking down ROR1 can reduce the anti-apoptotic and migratory potential of prostate cancer. Preliminary results indicate that knocking down ROR1 reduces the phosphorylation of AKT and GSK3ꞵ, which should lead to reduction in survival, migration, and cell cycle progression. Furthermore, knocking down ROR1 decreased migration, providing evidence that inhibition of the ROR1 molecular pathway is linked to reduction of cancerous phenotypes. These preliminary results indicate that ROR1 could be a novel molecular target that can be utilized for subtyping and treating prostate cancer.