EphB4 localises to the nucleus of prostate cancer cells

Mertens‐Walker, Inga; Lisle, Jessica; Nyberg, William A.; Stephens, Carson; Burke, Les J.; Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally‐Anne

doi:10.1016/j.yexcr.2015.02.015

Cited by 6 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, according to the online tool NLStradamus with default prediction cutoff of 0.5, the EPHB2 has a NLS between aa 1017-1033 corresponding to the aa sequence GKKKGMGKKKTDPGRGR. Otherwise, EPHB4 has been detected in the nucleus of prostate cancer cells [36] and other authors assure that presence of receptor tyrosine kinases in this cell compartment is possible [37] through several mechanisms including receptor internalization upon ligand binding and enzymatic cleavage. According to the free-prediction algorithm PsortII [38], EPHB2 could be present in the Golgi apparatus, endoplasmic reticulum and cell membrane in line with our results.…”

Section: Discussionmentioning

confidence: 99%

EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

et al. 2016

View full text Add to dashboard Cite

The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan® Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization.

show abstract

Section: Discussionmentioning

confidence: 99%

EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Then it travels back through the Golgi and endoplasmic reticulum to the nuclear membrane, where it travels through nuclear pores and is released from the membrane into the nucleoplasm by Sec61 ( Wang et al, 2010 ). Three other Eph receptors have recently been detected in the nuclei of cancer cell lines: EphA4 was detected in the nucleus of an osteosarcoma cell line, but its function is not known ( Kuroda et al, 2008 ); EphA5 was detected in the nucleus of lung cancer cell lines in response to ionizing radiation (IR), where it binds to ATM to repair DNA damage, preventing IR induced cell death ( Staquicini et al, 2015 ); and EphB4 was detected in the nucleus of prostate cancer cell lines, where it binds to DNA and alters transcriptional levels of genes associated with more advanced prostate cancer ( Mertens-Walker et al, 2015 ). Both EphA5 and EphB4 are present in the nucleus as full-length receptors ( Mertens-Walker et al, 2015 ; Staquicini et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Three other Eph receptors have recently been detected in the nuclei of cancer cell lines: EphA4 was detected in the nucleus of an osteosarcoma cell line, but its function is not known ( Kuroda et al, 2008 ); EphA5 was detected in the nucleus of lung cancer cell lines in response to ionizing radiation (IR), where it binds to ATM to repair DNA damage, preventing IR induced cell death ( Staquicini et al, 2015 ); and EphB4 was detected in the nucleus of prostate cancer cell lines, where it binds to DNA and alters transcriptional levels of genes associated with more advanced prostate cancer ( Mertens-Walker et al, 2015 ). Both EphA5 and EphB4 are present in the nucleus as full-length receptors ( Mertens-Walker et al, 2015 ; Staquicini et al, 2015 ). While the trafficking mechanism of EphA5 is not known, EphB4 has a bipartite nuclear localization sequence ( Mertens-Walker et al, 2015 ), similar to what we identified in EphA1, and is translocated into the nucleus with importin-α.…”

Section: Discussionmentioning

confidence: 99%

“…Both EphA5 and EphB4 are present in the nucleus as full-length receptors ( Mertens-Walker et al, 2015 ; Staquicini et al, 2015 ). While the trafficking mechanism of EphA5 is not known, EphB4 has a bipartite nuclear localization sequence ( Mertens-Walker et al, 2015 ), similar to what we identified in EphA1, and is translocated into the nucleus with importin-α. However, EphA5 and EphB4 are present at both the plasma membrane and the cytoplasm of lung cancer and prostate cancer cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species

et al. 2022

View full text Add to dashboard Cite

While the typical role of receptor tyrosine kinases is to receive and transmit signals at the cell surface, in some cellular contexts (particularly transformed cells) they may also act as nuclear proteins. Aberrant nuclear localization of receptor tyrosine kinases associated with transformation often enhances the transformed phenotype (i.e. nuclear ErbBs promote tumor progression in breast cancer). Rhabdomyosarcoma (RMS), the most common soft tissue tumor in children, develops to resemble immature skeletal muscle and has been proposed to derive from muscle stem/progenitor cells (satellite cells). It is an aggressive cancer with a 5-year survival rate of 33% if it has metastasized. Eph receptor tyrosine kinases have been implicated in the development and progression of many other tumor types, but there are only two published studies of Ephs localizing to the nucleus of any cell type and to date no nuclear RTKs have been identified in RMS. In a screen for protein expression of Ephs in canine RMS primary tumors as well as mouse and human RMS cell lines, we noted strong expression of EphA1 in the nucleus of interphase cells in tumors from all three species. This localization pattern changes in dividing cells, with EphA1 localizing to the nucleus or the cytoplasm depending on the phase of the cell cycle. These data represent the first case of a nuclear RTK in RMS, and the first time that EphA1 has been detected in the nucleus of any cell type.

show abstract

“…e overexpression of EPHB4 in colorectal cancer cells promotes its proliferation and migration, invasion, and angiogenesis [21,22]. EphB4 expression was too essentially higher in delicate tissue sarcomas, and mRNA and protein expression were altogether expanded in synovial sarcomas, while the regulation mechanism of EPHB4 still remains unknown [23]. In this experiment, the Edu incorporation assay method was conducted to detect the effects of miR-130-3p on cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

miR-130-3p Promotes MTX-Induced Immune Killing of Hepatocellular Carcinoma Cells by Targeting EPHB4

Shao

Ye²

2021

Journal of Healthcare Engineering

View full text Add to dashboard Cite

The vast majority of primary hepatocellular cancer is hepatocellular carcinomas (HCCs). Currently, HCC is one of the more common cancers in humans, and it has a high mortality and disability rate. Mitoxantrone (MTX) is an antitumor drug that can block type II topoisomerase. It has been reported that immunogenic cell death evoked by MTX can induce the discharge of damage associated with molecular patterns (DAMPs) and subsequently influence immune cell infiltration in the tumor microenvironment. High mobilities aggregation box 1 (HMGB1) is the prototypical extracellular DAMP. Many cellular processes have been reported to involve EPHB4 receptor tyrosine kinases, but the relation of DAMP and EPHB4 is uncertain. In this research, we assessed the impact of miR-130-3p by Edu incorporation test on cell proliferation, and we have proven its impact on HCC cell migration through Transwell and wound healing tests. Flow cytometry was applied to study its influence on apoptosis. Luciferase report test was integrated in detecting the miR-130-3p target gene. The influence of miR-130-3p on the manifestation of classical DAMPs was studied, such as HMGB1, ATP, and Calreticulin. A coculture experiment was carried out to further confirm its effects on immune cell infiltration. The result displayed that miR-130-3p overexpression considerably facilitates apoptosis and suppresses the migration or proliferation of HCC cells. EPHB4 was confirmed as the target gene of miR-130-3p. Overexpression of this target gene promotes emission of Calreticulin, ATP, and HMGB1 and subsequently promotes DCs maturation and proliferation of CD4+ T cells. In summary, our results demonstrated that miR-130-3p inhibits HCC cell proliferation and migration by targeting EPHB4 and promotes drug-induced immunogenic cell death.

show abstract

EphB4 localises to the nucleus of prostate cancer cells

Cited by 6 publications

References 50 publications

EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species

miR-130-3p Promotes MTX-Induced Immune Killing of Hepatocellular Carcinoma Cells by Targeting EPHB4

Contact Info

Product

Resources

About