ArticleCancer medicine2021
NOTCH3 limits the epithelial-mesenchymal transition and predicts a favorable clinical outcome in esophageal cancer.
Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Camrelizumab plus nimotuzumab as second-line therapy for advanced esophageal squamous cell carcinoma: a multicenter phase II study.Journal for immunotherapy of cancer · 2026Trial
- Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.Oncology reviews · 2026Review
- Primary cilia and cancer: a tale of many faces.Oncogene · 2025Review
- CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer.Cancers · 2025Article
- D-loop mutations in mitochondrial DNA are a risk factor for chemotherapy resistance in esophageal cancer.Scientific reports · 2024Article
- Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies.Biomolecules · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Extended Exposure Topotecan Significantly Improves Long-Term Drug Sensitivity by Decreasing Malignant Cell Heterogeneity and by Preventing Epithelial-Mesenchymal Transition.International journal of molecular sciences · 2023Article
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients.Open medicine (Warsaw, Poland) · 2022Article
- Epithelial-Mesenchymal Transition Gene Signature Is Associated with Neoadjuvant Chemoradiotherapy Resistance and Prognosis of Esophageal Squamous Cell Carcinoma.Disease markers · 2022Article
- Review
- Integrative genome-wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma.Cancer science · 2021Article
- Long Non-Coding RNA SNHG6 Supports Glioma Progression Through Upregulation of Notch1, Sox2, and EMT.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundEsophageal squamous cell carcinoma (ESCC) is the deadliest of all human squamous cell carcinomas and is characterized by chemotherapy resistance and poor prognosis associated with the epithelial-mesenchymal transition (EMT). A subset of ESCC displays loss-of-function mutations in genes encoding Notch receptor family members, including NOTCH3. Although Notch signaling regulates EMT in ESCC cells, the role of NOTCH3 in EMT and chemotherapy resistance remains elusive. This study aimed to examine the role of NOTCH3 in EMT and chemotherapy resistance, and determine whether NOTCH3 expression can be used to predict the response to chemotherapy.
methodsIn vitro and in vivo assays were conducted to clarify the contribution of NOTCH3 to chemotherapy resistance. Using specimens from 120 ESCC patients treated with neoadjuvant chemotherapy, we compared the expression levels of NOTCH3 and genes involved in EMT according to the degree of chemotherapy sensitivity.
resultsIn ESCC cells, chemotherapy resistance was associated with NOTCH3 downregulation and concurrent activation of EMT. RNA interference to silence NOTCH3 resulted in induction of the EMT marker Vimentin (VIM), leading to chemotherapy resistance in ESCC cells. Conversely, ectopic expression of the activated form of NOTCH3 suppressed EMT and sensitized cells to chemotherapy. Results of chromatin immunoprecipitation assays suggested that NOTCH3 may repress transcription of the VIM.
conclusionsOur findings suggest that NOTCH3 may control chemotherapy sensitivity by regulating EMT. NOTCH3 may serve as a novel biomarker to predict better clinical outcomes in ESCC patients.
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