ArticleCancer cell international2019
Mutual regulation of JAG2 and PRAF2 promotes migration and invasion of colorectal cancer cells uncoupled from epithelial-mesenchymal transition.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer.Cells, tissues, organs · 2021Pooled it
- Inhibiting METTL3 synergizes with Notch blockade to treat ESCC by targeting cancer stemness via m6A-JAG2.Journal of gastroenterology · 2026Article
- Review
- Dissecting regulated cell death states and transformation mechanisms in the evolutionary trajectory of 30 cancers.iScience · 2025Article
- PRAF2 as a novel biomarker for breast cancer with machine learning and experimentation validation.BMC cancer · 2025Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Osteosarcoma-Associated Immune Genes as Potential Immunotherapy and Prognosis Biomarkers.Biochemical genetics · 2024Article
- PRAF2 is an oncogene acting to promote the proliferation and invasion of breast cancer cells.Experimental and therapeutic medicine · 2022Article
- Extracellular vesicles and particles impact the systemic landscape of cancer.The EMBO journal · 2022Review
- Single-cell RNA-seq identification of four differentially expressed survival-related genes by a TARGET: Osteosarcoma database analysis.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- The prognostic value and immunological role of angiogenesis-related patterns in colon adenocarcinoma.Frontiers in oncology · 2022Article
- Angiogenesis-Related Molecular Subtypes and a Novel Prognostic Signature in Clear Cell Renal Cell Carcinoma Patients.International journal of general medicine · 2021Article
- Analysis of Circular RNA-Related Competing Endogenous RNA Identifies the Immune-Related Risk Signature for Colorectal Cancer.Frontiers in genetics · 2020Article
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8 authors at 1 institution in 1 country.
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Abstract
backgroundOur previous studies revealed that Jagged 2 (JAG2) is involved in the regulation of migration and invasion of colon cancer cells without affecting cell proliferation. This study further explored the specific mechanism by which JAG2 promotes migration and invasion of colorectal cancer cells.
methodsJAG2 mRNA expression in different clinical stages of colorectal cancer and normal intestinal tissues was detected by quantitative PCR (QPCR). QPCR and Western Blot were used to analyze the differential expression of JAG2 mRNA and protein between normal human colon tissue cells and various colorectal cancer cells. Co-expression status of JAG2 and epithelial-mesenchymal transition (EMT) markers in colon cancer tissues and cells was analyzed. The difference between TGF-β-induced EMT model and the JAG2 overexpression model were compared in promoting migration and invasion of HT29 cells. HT29 cells were treated with EMT pathway inhibitors (LY2157299 and Slug siRNA) to identify a cross-talk between the JAG2 effect and the Notch pathway. Co-expressed genes of JAG2 in colorectal cancer cells were identified using siRNA and transcriptome microarray technology. The mutual regulation of JAG2 and the co-expressed gene PRAF2 and the regulation of the paracrine effect of exosomes were analyzed.
resultsJAG2 was abnormally expressed in colorectal cancer tissues and directly related to clinical stages. Similar to the findings in tissues, the expression of both JAG2 mRNA and protein was significantly increased in the colorectal cancer cell lines compared with that of normal colorectal cell line CCD18-Co. It was shown in our cell model that JAG2 was involved in the regulation of migration and invasion independent of the canonical Notch signaling pathway. More interestingly, JAG2 also promoted the migration and invasion of colon cancer cells in a non-EMT pathway. Further analysis revealed the co-expression of JAG2 with PRAF2 in colorectal cancer cells. JAG2-rich exosomes were released from colorectal cancer cells in a PRAF2-dependent way, while these exosomes regulated the metastasis of colorectal cancer cells in a paracrine manner.
conclusionsThis is the evidence supporting the biological function of JAG2 through non-canonical Notch and non-EMT-dependent pathways and also the first demonstration of the functions of PRAF2 in colorectal cancer cells. These findings also provide theoretical basis for the development of small molecules or biological agents for therapeutic intervention targeting JAG2/PRAF2.
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