Ring Finger Protein 43 as a New Target for Cancer Immunotherapy

Uchida, Naotaka; Tsunoda, Takuya; Wada, Satoshi; Furukawa, Yoichi; Nakamura, Yusuke; Tahara, Hideaki

doi:10.1158/1078-0432.ccr-04-0104

Cited by 53 publications

(51 citation statements)

References 29 publications

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“…The proliferation and antiapoptotic effects of RNF43 have been well established in colorectal cancer (8,21). In keeping with previous reports, we found that knockdown of RNF43 by siRNA both inhibited proliferation and induced apoptosis in HCCs.…”

Section: Discussionsupporting

confidence: 92%

Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma

Xing

Zhou

Ding

et al. 2013

Molecular Cancer Therapeutics

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It has been shown that Ring finger protein 43 (RNF43) is overexpressed in colorectal cancer and mediates cancer cell proliferation; however, its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we found that RNF43 was frequently overexpressed in HCCs, and this overexpression was correlated with positive vascular invasion, poor tumor differentiation, and advanced tumor stage. Functional studies showed that knockdown of RNF43 could induce apoptosis and inhibit proliferation, invasion, colony formation, and xenograft growth of HCCs. Microarray-based gene profiling showed a total of 229 genes differentially expressed after RNF43 knockdown, many of which are involved in oncogenic processes such as cell proliferation, cell adhesion, cell motility, cell death, DNA repair, and so on. These results suggest that RNF43 is involved in tumorigenesis and progression of HCCs and that antagonism of RNF43 may be beneficial for HCC treatment.

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Section: Discussionsupporting

confidence: 92%

Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma

Xing

Zhou

Ding

et al. 2013

Molecular Cancer Therapeutics

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“…We examined whether CTLs could be induced with the peptide from human PBMCs. Monocyte-derived dendritic cells were used to induce CTLs against peptides as previously described (46,47). In brief, the PBMCs were obtained from healthy volunteers with corresponding HLAs and were cultured in the presence of granulocyte macrophage colony-stimulating factor (provided by Kirin Brewery Co., Tokyo, Japan) at 1,000 units/mL and interleukin-4 (Genzyme/Techne, Minneapolis, MN) at 1,000 units/mL.…”

Section: Methodsmentioning

confidence: 99%

“…Because we do not have access to A24/ Kb transgenic mice, we searched for class I epitopes restricted to HLA-A*2402 using only in vitro assays with human PBMCs as previously described (46). Epitope-candidate peptides were selected in the order of the binding scores, which reflected the binding affinity of the peptide to HLA class I molecules (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Tumor Growth with Antiangiogenic Cancer Vaccine Using Epitope Peptides Derived from Human Vascular Endothelial Growth Factor Receptor 1

Ishizaki¹,

Tsunoda²,

Wada³

et al. 2006

Clinical Cancer Research

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Purpose: Antiangiogenic therapy is now considered to be one of promising approaches to treat various types of cancer. In this study, we examined the possibility of developing antiangiogenic cancer vaccine targeting vascular endothelial growth factor receptor 1 (VEGFR1) overexpressed on endothelial cells of newly formed vessels in the tumor. Experimental Design: Epitope-candidate peptides were predicted from the amino acid sequence of VEGFR1 based on their theoretical binding affinities to the corresponding HLAs. The A2/Kb transgenic mice, which express the a1and a2 domains of human HLA-A*0201, were immunized with the epitope candidates to examine their effects. We also examined whether these peptides could induce human CTLs specific to the target cells in vitro.Results: The CTL responses in A2/Kb transgenic mice were induced with vaccination using identified epitope peptides restricted to HLA-A*0201. Peptide-specific CTL clones were also induced in vitro with these identified epitope peptides from peripheral blood mononuclear cells donated by healthy volunteers with HLA-A*0201. We established CTL clones in vitro from human peripheral blood mononuclear cells with HLA-A*2402 as well. These CTL clones were shown to have potent cytotoxicities in a HLA class I^restricted manner not only against peptide-pulsed target cells but also against target cells endogenously expressing VEGFR1. Furthermore, immunization of A2/Kb transgenic mice with identified epitope peptides restricted to HLA-A*0201 was associated with significant suppression of tumor-induced angiogenesis and tumor growth without showing apparent adverse effects. Conclusions:These results strongly suggest thatVEGFR1is a promising target for antiangiogenic cancer vaccine and warrants further clinical development of this strategy.

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“…RNF43 was also identified as a tumor-associated antigen of colorectal cancer (CRC). A tumor-associated antigen contains epitope peptides that promote antitumor immune response for cancer immunotherapy [14]. However, the role of RNF43 in the progression of carcinogenesis has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Shinada

Tsukiyama

Sho

et al. 2011

Biochemical and Biophysical Research Communications

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The ubiquitin-proteasomal system plays a crucial role in oncogenesis in colorectal tissues. Recent studies have shown that stability of -catenin, which functions as an oncogene for colorectal cancer, is regulated by ubiquitin-mediated degradation. It has been reported that a putative E3 ubiquitin ligase, RNF43, is highly expressed in human colorectal carcinoma and that RNF43 promotes cell growth. However, the involvement of RNF43 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (NEDL1), which enhances pro-apoptotic activity by p53. In addition, we found that RNF43 also interacts with p53 and that RNF43 suppresses transcriptional activity of p53 in H1299 cells and attenuates apoptosis induced by ultraviolet irradiation. These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis.3

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Ring Finger Protein 43 as a New Target for Cancer Immunotherapy

Cited by 53 publications

References 29 publications

Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma

Reversing Effect of Ring Finger Protein 43 Inhibition on Malignant Phenotypes of human Hepatocellular Carcinoma

Inhibition of Tumor Growth with Antiangiogenic Cancer Vaccine Using Epitope Peptides Derived from Human Vascular Endothelial Growth Factor Receptor 1

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

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