Inhibition of Wnt/β-Catenin Signaling Sensitizes Esophageal Cancer Cells to Chemoradiotherapy

Yue-Xi

Biotech and App Biochem

et al. 2023

To verify the inhibitory mechanism of β‐catenin‐designed peptides in colorectal cancer(CRC) tumors, the following experiments were performed. In vitro colony formation, Transwell assays, and flow cytometry were performed to assess the biological effects of designed peptides (F18KD, F20A4‐7k, F20A4‐10k, and F20A3‐9k + F20A4‐10k + F20A5‐9k) in HT‐29 cells. In vivo xenograft experiments were performed and treated with peptides. Next, tumors were subjected to Hematoxylin and eosin staining (HE), immunohistochemical, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays to evaluate the inhibitory effect of peptides on tumors. β‐Catenin levels were quantified via western blotting (WB) and quantitative real‐time polymerase chain reaction, and β‐catenin was located using confocal laser scanning microscopy. T‐cell factor‐4 (TCF‐4), C‐myc, and CCND1 levels were quantified via WB. Results were obtained as following. First, the peptides reduced viability, migration, and invasion; promoted apoptosis; and stabilized the S phase of HT‐29 cells. Second, peptides suppressed tumor growth and downregulated the expression of CD34, vascular endothelial growth factor, and β‐catenin in tumors. Furthermore, we found that peptides downregulated β‐catenin expression in both the cytoplasm and nucleus; TCF‐4, C‐myc, and CCND1 expression was also downregulated. Notably, β‐catenin‐targeting peptides had a better inhibitory effect on CRC than non‐β‐catenin‐target peptides, and a combination of peptides exerted a more potent inhibitory effect on CRC than single peptides. It suggested that β‐Catenin‐targeting peptides promote apoptosis in CRC tumors by inhibiting activation of the Wnt/β‐catenin pathway.

Section: Discussionmentioning

confidence: 80%

β‐Catenin‐treated peptides effectively inhibit the proliferation of colorectal cancer

Yue-Xi

Biotech and App Biochem

et al. 2023

“…As the key point of classical Wnt signaling pathway, CTNNB1 gene can bind with transcription factors TCF/LEF, thus forming a complex to promote the up-regulation of target genes, which finally causes a series of biological changes in cells and tissues ( Nabais et al, 2003 ; Wu et al, 2016a ). Through activation of Wnt signaling pathway, CTNNB1 involves in the early process of malignant tumors ( Spitzner et al, 2021 ; Yu et al, 2021 ), including liver cancer, gastric cancer and EC with high incidence, which are all present in ectopic expression of CTNNB1.…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a novel and superior protein risk model for prognosis prediction in esophageal cancer

Wang

et al. 2022

Front. Genet.

Esophageal cancer (EC) is recognized as one of the most common malignant tumors in the word. Based on the biological process of EC occurrence and development, exploring molecular biomarkers can provide a good guidance for predicting the risk, prognosis and treatment response of EC. Proteomics has been widely used as a technology that identifies, analyzes and quantitatively acquires the composition of all proteins in the target tissues. Proteomics characterization applied to construct a prognostic signature will help to explore effective biomarkers and discover new therapeutic targets for EC. This study showed that we established a 8 proteins risk model composed of ASNS, b-Catenin_pT41_S45, ARAF_pS299, SFRP1, Vinculin, MERIT40, BAK and Atg4B via multivariate Cox regression analysis of the proteome data in the Cancer Genome Atlas (TCGA) to predict the prognosis power of EC patients. The risk model had the best discrimination ability and could distinguish patients in the high- and low-risk groups by principal component analysis (PCA) analysis, and the high-risk patients had a poor survival status compared with the low-risk patients. It was confirmed as one independent and superior prognostic predictor by the receiver operating characteristic (ROC) curve and nomogram. K-M survival analysis was performed to investigate the relationship between the 8 proteins expressions and the overall survival. GSEA analysis showed KEGG and GO pathways enriched in the risk model, such as metabolic and cancer-related pathways. The high-risk group presented upregulation of dendritic cells resting, macrophages M2 and NK cells activated, downregulation of plasma cells, and multiple activated immune checkpoints. Most of the potential therapeutic drugs were more appropriate treatment for the low-risk patients. Through adequate analysis and verification, this 8 proteins risk model could act as a great prognostic evaluation for EC patients and provide new insight into the diagnosis and treatment of EC.

“…The Wnt/β-catenin signalling pathway has been found to be aberrantly activated in a variety of tumours. It has been demonstrated that inhibition of Wnt/β-catenin signalling increases the sensitivity of esophageal cancer cells to radiotherapy ( Spitzner et al, 2021 ). Cao et al (2020) used a high-resolution multiomics approach to map the epigenetic landscape of ESCC, suggesting that the epigenetically mediated Wnt/β-catenin signalling pathway is a potential oncogenic driver of ESCC.…”

Section: Epigenetically Linked Pathways In Esophageal Cancermentioning

confidence: 99%

Epigenetic modifications in esophageal cancer: An evolving biomarker

Zhao²,

Chen³

et al. 2023

Front. Genet.

Esophageal cancer is a widespread cancer of the digestive system that has two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In the diverse range of cancer therapy schemes, the side effects of conventional treatments remain an urgent challenge to be addressed. Therefore, the pursuit of novel drugs with multiple targets, good efficacy, low side effects, and low cost has become a hot research topic in anticancer therapy. Based on this, epigenetics offers an attractive target for the treatment of esophageal cancer, where major mechanisms such as DNA methylation, histone modifications, non-coding RNA regulation, chromatin remodelling and nucleosome localization offer new opportunities for the prevention and treatment of esophageal cancer. Recently, research on epigenetics has remained at a high level of enthusiasm, focusing mainly on translating the basic research into the clinical setting and transforming epigenetic alterations into targets for cancer screening and detection in the clinic. With the increasing emergence of tumour epigenetic markers and antitumor epigenetic drugs, there are also more possibilities for anti-esophageal cancer treatment. This paper focuses on esophageal cancer and epigenetic modifications, with the aim of unravelling the close link between them to facilitate precise and personalized treatment of esophageal cancer.