RETRACTED ARTICLE: Wilms tumor-suppressing peptide inhibits proliferation and induces apoptosis of Wilms tumor cells in vitro and in vivo

Results of immunotherapy in childhood solid cancer have been so far, with the exception of neuroblastoma, quite disappointing. Lack of knowledge of the immune contexture of these tumors may have contributed to the failure of immunotherapies so far. Here, we systematically reviewed the literature regarding the immunology of Wilms tumor (WT), one of the most frequent pediatric solid tumors of the abdomen. In Wilms tumor patients the high cure rate of >90%, achieved by the combination of surgery and radio-chemotherapy, is at the expense of a high early and late toxicity. Moreover, treatment-resistant entities, such as diffuse anaplastic tumors or recurrent disease, still pose unsolved clinical problems. Successful immunotherapy could represent a novel and possibly less-toxic treatment option. Employing the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) method of literature search, we analyzed the current knowledge of the immunological landscape of Wilms tumors in terms of tumor microenvironment, prognostic implications of single biomarkers, and immunotherapy response.

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“…Oncol. 2019 76 apoptosis-associated molecules (WTSP) IHC, cell culture, western blot 0 Ghanem et al. Br.…”

Section: Methodsmentioning

confidence: 99%

Systematic review of the immunological landscape of Wilms tumors

Palmisani

Kovar

Kager

et al. 2021

Molecular Therapy - Oncolytics

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“…These two forms of peptides play an important role in the body, participating in different physiological and pathological reactions. The levels of the peptide at m/z 6432 Da are significantly reduced in the serum of non-small cell lung cancer [7], papillary thyroid carcinoma [8], triple negative breast cancer [9], and nephroblastoma [4,10] patients compared to normal controls, indicating that it may be a potential biomarker for tumors. These specific protein markers play an important role in the diagnosis and treatment of malignant tumors [11].…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study identified a peptide (detected at m/z 6455.5 Da by proteomics) that is upregulated in healthy children and downregulated in Wilms tumors [4]. This peptide consists of 55 amino acids and is the smallest member of the apolipoprotein C family.…”

Section: Introductionmentioning

confidence: 99%

“…These specific protein markers play an important role in the diagnosis and treatment of malignant tumors [11]. For example, the peptide at m/z 6432 Da can inhibit the proliferation of nephroblastoma cells by regulating the Wnt/β-catenin pathway and has a potential antitumor effect [4]. Moreover, we found for the first time that the peptide at m/z 6432 Da can inhibit the proliferation of cervical cancer cells by regulating autophagy; thus, we temporarily named the peptide at m/z 6432 Da autophagy-related tumor suppressor peptide (ARCSP).…”

Section: Introductionmentioning

confidence: 99%

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Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway

Yang

Wang

Song

et al. 2020

J Exp Clin Cancer Res

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Background Autophagy is an intracellular process through which intracellular components are recycled in response to nutrient or growth factor deficiency to maintain homeostasis. We identified the peptide autophagy-related cancer-suppressing peptide (ARCSP), a potential antitumor peptide that disrupts intracellular homeostasis by blocking autophagic flux and causes cytotoxic death. Methods The proliferative ability of ARCSP-treated cervical cancer cells was examined by the CCK8, EdU, and colony formation assays. The TUNEL assay was used to detect apoptosis. Mitochondrial function was evaluated based on the mitochondrial membrane potential. Autophagic flux was detected by immunofluorescence and confocal microscopy. The autophagy-related proteins AMPK, Raptor, mTOR, p62, LC3B, atg7, Rab7, LAMP1, LAMP2, and cathepsin D were detected by Immunoblotting. The antitumor effect of ARCSP was explored in vivo by establishing a transplant tumor model in nude mice. Results The results demonstrated that ARCSP induced cell death and inhibited proliferation. ARCSP induced AMPK/mTOR activation, resulting in the accumulation of the proteins LC3B, p62 and Atg7. ARCSP also blocked autophagosome-lysosome fusion by inhibiting endosomal maturation and increasing the lysosomal pH. The accumulation of nonfused autophagosomes exacerbated cytotoxic death, whereas knocking down Atg7 reversed the cytotoxic death induced by ARCSP. ARCSP-treated cells exhibited increased cytotoxic death after cotreatment with an autophagy inhibitor (Chloroquine CQ). Furthermore, the tumors of ARCSP-treated nude mice were significantly smaller than those of untreated mice. Conclusions Our findings demonstrate that ARCSP, a novel lethal nonfused autophagosome inducer, might cause mitochondrial dysfunction and autophagy-related cytotoxic death and is thus a prospective agent for cancer therapy.

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“…The Wnt and PI3K/AKT signaling pathways are reported to be closely related to the development of nephroblastoma ( 20 ). AKT serves an important role in a variety of interrelated cellular signaling mechanisms involved in cellular metabolism, growth and division, the inhibition of apoptosis and angiogenesis ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway

Qian

Liu

2021

Mol Med Rep

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Forkhead transcription factor O subfamily 3A (FOXO3a) is an important tumor suppressor gene that is expressed in renal tissue and has been reported to be downregulated in clear cell renal cell carcinoma (CCRCC). Notably, the overexpression of FOXO3a was previously discovered to inhibit the progression of CCRCC. However, the expression levels of FOXO3a in nephroblastoma cell lines remain unknown. The present study aimed to investigate the expression levels of FOXO3a in nephroblastoma cell lines and to determine the mechanism of action of the biological functions of FOXO3a. Western blotting and reverse transcription-quantitative PCR were used to analyze the expression levels of FOXO3a in nephroblastoma cell lines. Subsequently, the effects of the overexpression of FOXO3a and the genetic knockdown of the Wnt/β-catenin signaling protein Axin-2 on the biological functions were determined through Cell Counting Kit-8, cell colony formation assays, scratch and Transwell assay and flow cytometric analysis experiments. The expression levels of FOXO3a were discovered to be downregulated in nephroblastoma cell lines. The overexpression of FOXO3a inhibited the proliferation, invasion and migration of nephroblastoma cells, while inducing apoptosis. Furthermore, the overexpression of FOXO3a downregulated the expression levels of β-catenin and Cyclin-D1 proteins involved in the Wnt/β-catenin signaling pathway. Cell proliferation and the migration and invasion ability of 17–94 cells in shRNA-Axin2-2 group were promoted. Cell apoptosis was predominantly increased by overexpressed FOXO3a, which was reversed by shRNA-Axin2-1. The biological effects of overexpressing FOXO3a on nephroblastoma were reversed after activation of Wnt/β-catenin. In conclusion, the findings of the present study suggested that FOXO3a may inhibit nephroblastoma cell proliferation, migration and invasion, while inducing apoptosis, by downregulating the Wnt/β-catenin signaling pathway. These results may provide a novel method for the early diagnosis and precise treatment of nephroblastoma.

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RETRACTED ARTICLE: Wilms tumor-suppressing peptide inhibits proliferation and induces apoptosis of Wilms tumor cells in vitro and in vivo

Cited by 5 publications

References 26 publications

Systematic review of the immunological landscape of Wilms tumors

Systematic review of the immunological landscape of Wilms tumors

Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway

FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway

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