Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2

Abstract

Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor which has previously been shown to be expressed in a variety of cancers. HDGF over-expression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is over-expressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1 and PC-3 cells. Forced over-expression enhanced cell viability of RWPE-1 cells, while HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival related protein as ectopic over-expression of HDGF in RWPE cells up-regulated the expression of anti-apoptosis proteins cyclin E and BCL-2, while simultaneously down-regulating pro-apoptotic protein BAX. Western blot analysis also showed that HDGF over-expression modulated the activity of phospho AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k2, showing reduced cell proliferation as well as inhibition of NF-kB expression in HDGF over-expressed RWPE cells treated with a HDGF monoclonal antibody and vitamin K2. Collectively, our results suggest that HDGF is a relevant protein in prostate oncogenesis and may serve as a potential therapeutic target in prostate cancer.

Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9

“…Moreover, HDGF involves in the aggressive biological properties, including invasiveness [ 26 ], angiogenesis [ 28 ] and metastasis [ 18 ] of cancer cells. In PCa, HDGF is overexpressed in DU145, PC3 and LNCaP cells compared with the normal prostate cell RWPE-1 [ 30 ] and down-regulation of HDGF expression inhibits the proliferation of PCa DU145, PC3 and LNCaP cells [ 23 , 30 ], and the migration and invasion of DU145 cells [ 23 ]. Moreover, up-regulation of HDGF expression in normal RWPE-1 prostate cell facilitates the migration and invasion of RWPE-1 cells [ 30 ].…”

“…In PCa, HDGF is overexpressed in DU145, PC3 and LNCaP cells compared with the normal prostate cell RWPE-1 [ 30 ] and down-regulation of HDGF expression inhibits the proliferation of PCa DU145, PC3 and LNCaP cells [ 23 , 30 ], and the migration and invasion of DU145 cells [ 23 ]. Moreover, up-regulation of HDGF expression in normal RWPE-1 prostate cell facilitates the migration and invasion of RWPE-1 cells [ 30 ]. However, the underlying molecular mechanism associated with HDGF-mediated cell migration and invasion in PCa remains elusive.…”

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

“…Immunofluorescence was performed based on our previous protocol (Shetty et al, 2016). Briefly, cervical cancer cells (HeLa and SiHa) were cultured on eight‐chamber plates, treated with Nef (25 μM), and incubated at 37°C and 5% CO 2 for 48 hr.…”

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions

“…The HDGF family of chromatin binding proteins, which in addition to DFS70/LEDGF also includes HDGF, HRP2/HDGF2 (HDGF-related protein 2), HRP-3, and HDGF-L1, has been implicated in promoting cancer cell proliferation and survival [33][34][35]. These proteins share significant sequence homology, particularly in the N-terminal region, which contains a 100 amino acid stretch called the HATH (homologous to the amino terminus of HDGF) domain.…”