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

Abstract

Metastasis is the primary cause of prostate cancer (CaP)-related death. We investigate the molecular, pathologic and clinical outcome associations of EphA6 expression and CaP metastasis. The expression profiling of Eph receptors (Ephs) and their ephrin ligands was performed in parental and metastatic CaP cell lines. Among Ephs and ephrins, only EphA6 is consistently overexpressed in metastatic CaP cells. Metastatic potential of EphA6 is assessed by RNAi in a CaP spontaneous metastasis mouse model. EphA6 knock-down in human PC-3M cells causes decreased invasion in vitro and reduced lung and lymph node metastasis in vivo. In addition, knock-down of EphA6 decreases tube formation in vitro and angiogenesis in vivo. EphA6 mRNA expression is higher in 112 CaP tumor samples compared with benign tissues from 58 benign prostate hyperplasia patients. Positive correlation was identified between EphA6 expression and vascular invasion, neural invasion, PSA level, and TNM staging in CaP cases. Further, genome-wide gene expression analysis in EphA6 knock-down cells identified a panel of differentially regulated genes including PIK3IPA, AKT1, and EIF5A2, which could contribute to EphA6-regulated cancer progression. These findings identify EphA6 as a potentially novel metastasis gene which positively correlates with CaP progression. EphA6 may be a therapeutic target in metastatic CaP.

Knockdown of GSG2 inhibits prostate cancer progression in�vitro and in�vivo

“…The results revealed that knockdown of GSG2 inhibited the phosphorylation of EphA4, EphA5, EphA6, EphA7, EphB3, FER, IGF-IR, Itk, JAK2, JAK3, LTK, Lyn, M-CSFR, MUSK, NGFR, PDGFR-α, ROS, SRMS, TXK, Tyk2 and ZAP70 in PCa cells compared with those infected with shCtrl. According to previous studies, EphA4, EphA5, EphA6 and EphA7 promote angiogenesis and PCa metastasis, and are associated with human PCa progression (29,(31)(32)(33). FER kinase serves a central role in breast cancer metastasis and PCa cell proliferation (34).…”

Eukaryotic translation initiation factor 5A2 is highly expressed in prostate cancer and predicts poor prognosis

“…It was reported that EIF5A2 was up-regulated in ovary cancer (15), nasopharyngeal carcinoma (16), colorectal carcinoma (17), hepatocellular carcinoma (18), gastric cancer (19) and non-small cell lung cancer (20). A previous study by Li et al (21), revealed that EIF5A2 was significantly decreased in prostate cancer when Ephrin type-A receptor 6 was knocked down. However, the expression type of EIF5A2 in prostate cancer cells or tissues, and clinical significance of EIF5A2 have not yet been investigated.…”

Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells

“…EIF5A2 has been implicated in a number of cancers, including bladder cancer, colorectal cancer, pancreatic adenocarcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, breast cancer, prostate adenocarcinoma, hepatocellular carcinoma, ovarian cancer and melanoma (9,(14)(15)(16)(17)(18)(19)(20)(21)(22). Patients with esophageal squamous cell carcinoma, bladder cancer and pancreatic adenocarcinoma in which EIF5A2 is overexpressed have been demonstrated to exhibit statistically significantly shorter survival times (14,17,20).…”