Bone marrow (BM) samples of 52 NB patients were assessed for the expression of β-catenin by immunohistochemistry (IHC), and PHOX2B by real time PCR (RT-PCR), compared to 12 healthy normal controls (NC).
Recent studies in mouse neuroblastoma cells (Neuro-2A) demonstrated ORF2 interacts with β-catenin and a β-catenin coactivator, high-mobility group AT-hook 1 (HMGA1) protein, which correlates with increased β-catenin-dependent transcription and cell survival.
Overall, our results define an oncogenic role of <i>pancEts-1</i> in neuroblastoma progression through hnRNPK-mediated β-catenin stabilization, with potential implications for the clinical therapeutics of neuroblastoma.<b>Significance:</b> These findings reveal the oncogenic functions of a long noncoding RNA in neuroblastoma progression, offering a potential target for clinical therapeutics.<i></i>.
Assessment of β-catenin immunohistochemistry shows high levels of β-catenin in tumours with better differentiation, further supporting a role for canonical Wnt signalling in neuroblastoma differentiation.
In support of this hypothesis, coimmunoprecipitation studies demonstrated that ORF2 stably interacts with a complex containing β-catenin and/or HMGA1 in transfected mouse neuroblastoma (Neuro-2A) cells.
We recently published that the crizotinib sensitivity in NB cells strongly correlates with the crizotinib-ALK binding, and β-catenin effectively hinders this interaction and confers crizotinib resistance.
Inhibition of Rho-associated kinases (ROCKs) that are important in mediating non-canonical Wnt signaling resulted in increased expression of Prickle1 and inhibition of β-catenin activity in neuroblastoma cells.
Ectopic expression of a degradation-resistant β-catenin mutant enhances neuroblastoma cell viability and inhibition of β-catenin with XAV939 prevented PGE2 -induced cell viability.
β-Catenin knockdown could effectively control growth of neuroblastoma cells in vitro and in nude mice, suggesting that targeting β-catenin may be useful in clinical control of neuroblastoma.
We used the SH-SY5Y human neuroblastoma cell line and treated the cells with melatonin and then exposed them to the prion protein, PrP, or the β-catenin inhibitor, ICG-001.
We found that IL-24 effectively inhibits SH-SY5Y neuroblastoma cell migration and invasion by changing subcellular localization and cellular levels of β-catenin and regulating the levels of proteins associated with cell migration and invasion.
Indeed, we found that the amount of β-catenin in nucleus, which indicated the activation of Wnt/β-catnin signaling, was accumulated in human neuroblastoma specimens and positively correlated with clinical risk of neuroblastoma.
Our data represent the first implication of the Wnt/beta-catenin pathway in NB chemoresistance and identify potential new targets to treat aggressive and resistant NB.
Our objective was to explore the novel role that Wnt/beta-catenin plays in human neuroblastoma cell line SH-SY5Y, including detection of expression of wnt1 and beta-catenin in SH-SY5Y, and the morphological and proliferative changes after Wnt1 RNAi in SH-SY5Y.
More directly, Patterns of Gene Expression and Gene Set Enrichment Analyses demonstrated beta-catenin target genes (for example, MYC, PPARD, NRCAM, CD44, TCF7) as coordinately upregulated in high-risk NBs without MYCN amplification in comparison to high-risk MYCN-amplified or intermediate-risk NBs, supporting pathway activation in this subset.
We overexpressed beta-catenin into a human neuroblastoma cell line NB-1 and observed its effect on cellular morphology, growth potential and alteration in a known differentiation related gene, trkA.
Since activated microglia and astrocytes play a role in the process of neuronal degeneration in AD, the cytokine/growth factor-regulated expression of beta-catenin in human neural cell lines, including NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N), IMR-32 neuroblastoma, SKN-SH neuroblastoma and U-373MG astrocytoma, was studied quantitatively following exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (cAMP) (dbcAMP) or phorbol 12-myristate 13-acetate (PMA).