EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes cancer cell growth

Iiizumi, Megumi; Hosokawa, Munetaka; Takehara, Akio; Chung, Suyoun; Nakamura, Tõru; Katagiri, Toyomasa; Eguchi, Hidetoshi; Ohigashi, Hajime; Ishikawa, Osamu; Nakamura, Yusuke; Nakagawa, Hidewaki

doi:10.1111/j.1349-7006.2006.00313.x

Cited by 62 publications

(54 citation statements)

References 35 publications

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“…However, expression of ephrin ligands was not clearly concordant with that of EphA4 in cancer tissue samples. On the other hand, coexpression of ephrinA3 and EphA4 has been reported to play an important role in pancreatic cancer [19] . These results further support the notion that combinations for the Eph receptors and ephrin ligands depend on tissue-type and/or cancertype [7][8][9][10] .…”

Section: Discussionmentioning

confidence: 99%

“…Previous microarray and Northern blot analyses have shown that EphA4 expression in normal adult tissues is very restricted [19] . Moreover, overexpression of EphA4 in gastric cancer was observed at the protein level as analyzed by immunohistochemistry and this correlated with depth of invasion.…”

Section: Discussionmentioning

confidence: 99%

“…These results further support the notion that combinations for the Eph receptors and ephrin ligands depend on tissue-type and/or cancertype [7][8][9][10] . Moreover, the interaction of EphA4 expressed on gastric cancer cells and ephrin ligands expressed on nontumour cells, such as mesenchymal cells and vascular cells, could play a role in gastric cancer through the interaction between these cells [19] . Further studies are necessary to clarify these issues.…”

Section: Discussionmentioning

confidence: 99%

“…The primer sequences used were 5'-CGT-TATGTGGGAAGTGATGTCATA-3' and 5'-TTCCT-CAATGGCTTTAATCACA TCT-3' for EphA4 [9] and 5'-TCCTAGTGCCACAATCCCAGTCCT-3' and 5'-AGGGCATTAGAGGCCCAGAGA-3' for FGFR1 [23] . The other primer sequences were provided by Dr. Nakagawa [19] . Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) served as an internal control of the reaction.…”

Section: Semiquantitative Rt-pcr and Real-time Rt-pcrmentioning

confidence: 99%

“…Compared with other Eph receptors, EphA4 is distinguished by its ability to bind to both type A ephrins and most type B ephrins [7][8][9][10] . Indeed, overexpression of EphA4 has been recently reported in human prostate and pancreatic cancers [18,19] . Moreover, it has been reported that EphA4 forms a hetero receptor complex with fibroblast growth factor receptor (FGFR) 1 and that EphA4/FGFR1 complex potentiates FGFR-mediated downstream signal transduction.…”

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confidence: 99%

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Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

Oki¹,

Yamamoto²,

Taniguchi³

et al. 2008

WJG

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recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth. CONCLUSION: Our results suggest that overexpression of EphA4 plays a role in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Semiquantitative Rt-pcr and Real-time Rt-pcrmentioning

confidence: 99%

mentioning

confidence: 99%

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Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

Oki¹,

Yamamoto²,

Taniguchi³

et al. 2008

WJG

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EphrinA3 is a key regulator of malignant behaviors and a potential prognostic factor in lung adenocarcinoma

et al. 2022

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Background: As a member of the Ephrin protein family that elicits short distance cell-cell signaling, EphrinA3 has been shown to promote or inhibit tumorigenesis depending on tumor types, but its roles and the underlying mechanisms in lung adenocarcinoma (LUAD) have not been reported. Materials and Methods:The TCGA database and Kaplan-Meier Plotter database were used to analyze the differential expression of EphrinA3 between LUAD and para-carcinoma tissues, and its effect on overall survival of LUAD patients. CCK-8 assay, Edu assay, and flow cytometry were used to probe the effect of EphrinA3 on the proliferation of LUAD cells, and transwell assay was employed to examine its effect on migration and invasion. In addition, the effect of EphrinA3 on the growth of LUAD was further evaluated using a xenograft tumor model. Results: EphrinA3 was expressed highly in LUAD, and its expression level was negatively correlated with the prognosis of LUAD patients. In addition, EphrinA3 promoted proliferation, migration, and invasion of LUAD cells, and accelerated tumor growth in a xenograft LUAD model. The reported EphrinA3 receptors, EphA1 and EphA10, were expressed in clinical LUAD tissues and co-localized with EphrinA3 in LUAD cells. Mechanistically, EphrinA3/Eph signaling activated AKT, ERK, and p38MAPK, induced epithelial-mesenchymal transition (EMT), and upregulated matrix metalloproteases-2 and -9 (MMP-2/−9). Conclusion: EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.

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C12orf48, termed PARP‐1 binding protein, enhances poly(ADP‐ribose) polymerase‐1 (PARP‐1) activity and protects pancreatic cancer cells from DNA damage

Piao

Nakagawa

Ueda

et al. 2010

Genes Chromosomes & Cancer

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To identify novel therapeutic targets for aggressive and therapy-resistant pancreatic cancer, we had previously performed expression profile analysis of pancreatic cancers using microarrays and found dozens of genes trans-activated in pancreatic ductal adenocarcinoma (PDAC) cells. Among them, this study focused on the characterization of a novel gene C12orf48 whose overexpression in PDAC cells was validated by Northern blot and immunohistochemical analysis. Its overexpression was observed in other aggressive and therapy-resistant malignancies as well. Knockdown of C12orf48 by siRNA in PDAC cells significantly suppressed their growth. Importantly, we demonstrated that C12orf48 protein could directly interact with Poly(ADP-ribose) Polymerase-1 (PARP-1), one of the essential proteins in the repair of DNA damage, and positively regulate the poly(ADP-ribosyl)ation activity of PARP-1. Depletion of C12orf48 sensitized PDAC cells to agents causing DNA damage and also enhanced DNA damage-induced G2/M arrest through reduction of PARP-1 enzymatic activities. Hence, our findings implicate C12orf48, termed PARP-1 binding protein (PARPBP), or its interaction with PARP-1 to be a potential molecular target for development of selective therapy for pancreatic cancer.

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EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes cancer cell growth

Abstract: To isolate novel diagnostic markers and drug targets for pancreatic ductal adenocarcinoma (PDAC),

Cited by 62 publications

References 35 publications

Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

EphrinA3 is a key regulator of malignant behaviors and a potential prognostic factor in lung adenocarcinoma

C12orf48, termed PARP‐1 binding protein, enhances poly(ADP‐ribose) polymerase‐1 (PARP‐1) activity and protects pancreatic cancer cells from DNA damage

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