EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression

ABSTRACT: Purpose: Metastasis remains the primary cause of prostate cancer (CaP) related death. Here, we investigate the molecular, pathologic, and clinical outcome associations of EphA6 expression and its role in CaP progression and metastasis.Experimental Design: The gene expression profiling of Eph receptors (Ephs) and their ephrin ligands was performed in CaP cell lines by real-time RT-PCR. Metastatic potential of EphA6 gene was analyzed by RNAi approaches in a spontaneous CaP mouse model. The mRNA expression of EphA6 was measured in 58 benign prostate hyperplasia (BPH) and 112 CaP samples. Results: Among the tested Ephs and ligands, EphA6 is the only consistently overexpressed member in CaP lymph node metastatic cells. EphA6 knock-down (KD) in human PC-3M cells causes decreased invasion in vitro and reduced lung and lymph node metastasis in vivo. In addition, KD of EphA6 decreases tube formation in vitro and angiogenesis in vivo. Studies on the clinical samples demonstrate that EphA6 is overexpressed in the CaP tumor tissues compared with those from BPH patients. The correlation was identified between EphA6 expression and vascular invasion (P=0.004), neural invasion (P=0.002), PSA level (P=0.013), and TNM staging (P=0.021) in 112 CaP cases.Further, genome-wide gene expression analysis in KD of EphA6 cells identified a panel of genes, such as PIK3IPA, AKT1, and EIF5A2, which could be associated with EphA6-regulated cancer progression. Conclusions: These findings identify EphA6 as a potentially novel metastasis gene, and increased EphA6 mRNA expression positively correlates with CaP progression. The mechanisms to inhibit EphA6 expression might suppress CaP metastatic aggressiveness. Knock-down of EphA6 induced gene expression in human prostate cell:PC-3M/shEphA6-1, PC3M/shControl, CWR22rv1/shEphA6-1, and CWR22rv1/shControl cell line.

ORGANISM(S): Homo sapiens

SUBMITTER: shibao li 

PROVIDER: E-GEOD-66335 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress