ArticleMolecular and cellular biology2014
The apoptosis repressor with a CARD domain (ARC) gene is a direct hypoxia-inducible factor 1 target gene and promotes survival and proliferation of VHL-deficient renal cancer cells.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 42 citations in OpenAlex.
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma.Journal of biomedical science · 2025Review
- Role of apoptosis repressor with caspase recruitment domain in human health and chronic diseases.Annals of medicine · 2024Review
- GJA4 expressed on cancer associated fibroblasts (CAFs)-A 'promoter' of the mesenchymal phenotype.Translational oncology · 2024Article
- HIF-1α promotes kidney organoid vascularization and applications in disease modeling.Stem cell research & therapy · 2023Article
- A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.Apoptosis : an international journal on programmed cell death · 2023Review
- No Time to Die: How Kidney Cancer Evades Cell Death.International journal of molecular sciences · 2022Review
- Synthetic lethality of cyclin-dependent kinase inhibitor Dinaciclib withCell cycle (Georgetown, Tex.) · 2022Article
- Identifying genetic variants for age of migraine onset in a Han Chinese population in Taiwan.The journal of headache and pain · 2021Article
- The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis.Cell death & disease · 2021Article
- Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.Cancer cell international · 2019Article
- TRIM32 promotes cell proliferation and invasion by activating β-catenin signalling in gastric cancer.Journal of cellular and molecular medicine · 2018Article
- Renal Cell Carcinoma: Molecular Aspects.Indian journal of clinical biochemistry : IJCB · 2018Review
- Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields.Cell death & disease · 2018Review
- CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage.Nucleic acids research · 2017Article
- Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.Oncogene · 2017Article
- Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow.Nature cell biology · 2016Article
- Genomic and functional analysis of the host response to acute simian varicella infection in the lung.Scientific reports · 2016Article
- CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer.Oncogene · 2016Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
The induction of hypoxia-inducible factors (HIFs) is essential for the adaptation of tumor cells to a low-oxygen environment. We found that the expression of the apoptosis inhibitor ARC (apoptosis repressor with a CARD domain) was induced by hypoxia in a variety of cancer cell types, and its induction is primarily HIF1 dependent. Chromatin immunoprecipitation (ChIP) and reporter assays also indicate that the ARC gene is regulated by direct binding of HIF1 to a hypoxia response element (HRE) located at bp -190 upstream of the transcription start site. HIFs play an essential role in the pathogenesis of renal cell carcinoma (RCC) under normoxic conditions, through the loss of the Von Hippel-Lindau gene (VHL). Accordingly, our results show that ARC is not expressed in normal renal tissue but is highly expressed in 65% of RCC tumors, which also express high levels of carbonic anhydrase IX (CAIX), a HIF1-dependent protein. Compared to controls, ARC-deficient RCCs exhibited decreased colony formation and increased apoptosis in vitro. In addition, loss of ARC resulted in a dramatic reduction of RCC tumor growth in SCID mice in vivo. Thus, HIF-mediated increased expression of ARC in RCC can explain how loss of VHL can promote survival early in tumor formation.
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