ArticleMolecular and cellular biochemistry2013
ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway.
Article in Molecular and cellular biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids.Scientific reports · 2024Article
- Chronic intermittent hypoxia facilitates the development of angiotensin II-induced abdominal aortic aneurysm in male mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Characterization of EpCAM in thyroid cancer biology by three-dimensional spheroids in vitro model.Cancer cell international · 2024Article
- Unraveling the role of ADAMs in clinical heterogeneity and the immune microenvironment of hepatocellular carcinoma: insights from single-cell, spatial transcriptomics, and bulk RNA sequencing.Frontiers in immunology · 2024Article
- Investigation on acquired palbociclib resistance by LC-MS based multi-omics analysis.Frontiers in molecular biosciences · 2023Article
- ADAM10 and ADAM17-Novel Players in Retinoblastoma Carcinogenesis.International journal of molecular sciences · 2022Article
- Head and Neck Squamous Cell Carcinoma: Risk Factors, Molecular Alterations, Immunology and Peptide Vaccines.International journal of peptide research and therapeutics · 2022Review
- ADAM and ADAMTS Proteins, New Players in the Regulation of Hepatocellular Carcinoma Microenvironment.Cancers · 2021Review
- ADAM17 Mediates Hypoxia-Induced Keratinocyte Migration via the p38/MAPK Pathway.BioMed research international · 2021Article
- Fractalkine/CX3CL1 in Neoplastic Processes.International journal of molecular sciences · 2020Review
- Blood flow restriction exercise stimulates mobilization of hematopoietic stem/progenitor cells and increases the circulating ACE2 levels in healthy adults.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Hypoxic regulation of angiotensin-converting enzyme 2 and Mas receptor in human CD34Journal of cellular physiology · 2019Article
- Review
- miRNA-20b inhibits cerebral ischemia-induced inflammation through targeting NLRP3.International journal of molecular medicine · 2019Article
- hnRNPM induces translation switch under hypoxia to promote colon cancer development.EBioMedicine · 2019Article
- Inhibition of hepatocellular carcinoma cell proliferation, migration, and invasion by a disintegrin and metalloproteinase-17 inhibitor TNF484.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2019Article
- [ADAM17 knockdown increases sensitivity of SW480 cells to cetuximad].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- BHLHE40 confers a pro-survival and pro-metastatic phenotype to breast cancer cells by modulating HBEGF secretion.Breast cancer research : BCR · 2018Article
- ADAM17 inhibition enhances platinum efficiency in ovarian cancer.Oncotarget · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A disintegrin and metalloproteinase-17 (ADAM17) is a member of the metalloproteinase superfamily and involved in the cleavage of ectodomain of many transmembrane proteins. ADAM17 is overexpressed in a variety of human tumors, which is associated with tumor development and progression. In the present study, we sought to investigate the expression and function of ADAM17 in hypoxia-treated hepatocellular carcinoma (HCC) cells. Western blot analysis was used to measure the expression of ADAM17 in HCC cell lines (Hep3B and HepG2 cells). Annexin V/PI double staining was performed to analyze the effects of ADAM17 on hypoxia-mediated cisplatin resistance. ADAM17 expression was upregulated by hypoxia treatment in HCC cells at both mRNA and protein levels. Overexpression of ADAM17 reduced cisplatin-induced apoptosis in HCC cells, accompanies by less cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Forced expression of ADAM17 enhanced the phosphorylation of epidermal growth factor receptor (EGFR) and Akt without affecting the expression of total EGFR and Akt. Pretreatment with EGFR inhibitor AG1478 or phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 rescued ADAM17-mediated cisplatin resistance of HCC cells. ADAM17 silencing attenuated hypoxia-induced cisplatin resistance and enhanced the accumulation of cleaved caspase-3 and PARP. Western blot analysis showed that overexpression of hypoxia-inducible factor-1α (HIF-1α), a transcription factor, upregulated the expression of ADAM17 and HIF-1α silencing downregulated the expression of ADAM17 in hypoxia-treated HCC cells, indicating the regulation of ADAM17 by HIF-1α. Taken together, our results indicated that ADAM17 is upregulated by hypoxia and contributes to hypoxia-induced cisplatin resistance via EGFR/PI3K/Akt pathway.
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