ArticleStem cells translational medicine2016
A Disintegrin and Metalloproteinase Domain 17 Regulates Colorectal Cancer Stem Cells and Chemosensitivity Via Notch1 Signaling.
Article in Stem cells translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Dysregulated NF-κB-Dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T-cell Responses in Patients with Melanoma.Cancer immunology research · 2020Trial
- Review
- A disintegrin and metallopeptidase domain (ADAM) 12, ADAM 17 mRNA and ADAM10 protein hold potential as biomarkers for detection of early gastric cancer.Scientific reports · 2025Article
- Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity.Frontiers in cell and developmental biology · 2023Review
- Liver Endothelium Promotes HER3-Mediated Cell Survival in Colorectal Cancer with Wild-Type and Mutant KRAS.Molecular cancer research : MCR · 2022Article
- Liver Endothelium Microenvironment Promotes HER3-mediated Cell Growth in Pancreatic Ductal Adenocarcinoma.Journal of cancer science and clinical therapeutics · 2022Article
- Proteases Regulate Cancer Stem Cell Properties and Remodel Their Microenvironment.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Review
- Extracellular Matrix Biomarkers in Colorectal Cancer.International journal of molecular sciences · 2021Review
- Article
- Sex-Biased Gene Expression ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion.Molecular cancer research : MCR · 2019Article
- Doublecotin-Like Kinase 1 Increases Chemoresistance of Colorectal Cancer Cells through the Anti-Apoptosis Pathway.Journal of stem cell research & therapy · 2019Article
- A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo.Cell proliferation · 2018Article
- Role of ADAM10 in intestinal crypt homeostasis and tumorigenesis.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Endothelial cells activate the cancer stem cell-associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion.Molecular oncology · 2017Article
- Overexpression of PER3 Inhibits Self-Renewal Capability and Chemoresistance of Colorectal Cancer Stem-Like Cells via Inhibition of Notch and β-Catenin Signaling.Oncology research · 2017Article
- Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2017Article
- ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Th17 cell-derived IL-17A promoted tumor progression via STAT3/NF-κB/Notch1 signaling in non-small cell lung cancer.OncoimmunologyArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Evidence is accumulating for the role of cancer stem cells (CSCs) in mediating chemoresistance in patients with metastatic colorectal cancer (mCRC). A disintegrin and metalloproteinase domain 17 (ADAM17; also known as tumor necrosis factor-α-converting enzyme [TACE]) was shown to be overexpressed and to mediate cell proliferation and chemoresistance in CRC cells. However, its role in mediating the CSC phenotype in CRC has not been well-characterized. The objective of the present study was to determine whether ADAM17 regulates the CSC phenotype in CRC and to elucidate the downstream signaling mechanism that mediates cancer stemness. We treated established CRC cell lines and a newly established human CRC cell line HCP-1 with ADAM17-specific small interfering RNA (siRNA) or the synthetic peptide inhibitor TAPI-2. The effects of ADAM17 inhibition on the CSC phenotype and chemosensitivity to 5-fluorouracil (5-FU) in CRC cells were examined. siRNA knockdown and TAPI-2 decreased the protein levels of cleaved Notch1 (Notch1 intracellular domain) and HES-1 in CRC cells. A decrease in the CSC phenotype was determined by sphere formation and ALDEFLUOR assays. Moreover, TAPI-2 sensitized CRC cells to 5-FU by decreasing cell viability and the median lethal dose of 5-FU and increasing apoptosis. We also showed the cleavage and release of soluble Jagged-1 and -2 by ADAM17 in CRC cells. Our studies have elucidated a role of ADAM17 in regulating the CSC phenotype and chemoresistance in CRC cells. The use of drugs that inhibit ADAM17 activity might increase the therapeutic benefit to patients with mCRC and, potentially, those with other solid malignancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.