ArticleInternational journal of oncology2014
HAF drives the switch of HIF-1α to HIF-2α by activating the NF-κB pathway, leading to malignant behavior of T24 bladder cancer cells.
Article in International journal of oncology, 2014. 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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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Cross-talk between Pseudomonas aeruginosa and urinary tract infections.World journal of urology · 2025Review
- L-Theanine Mitigates Acute Alcoholic Intestinal Injury by Activating the HIF-1 Signaling Pathway to Regulate the TLR4/NF-κB/HIF-1α Axis in Mice.Nutrients · 2025Article
- Modulating Nucleus Oxygen Concentration by Altering Intramembrane Cholesterol Levels: Creating Hypoxic Nucleus in Oxic Conditions.International journal of molecular sciences · 2022Article
- Tenascin-C promotes bladder cancer progression and its action depends on syndecan-4 and involves NF-κB signaling activation.BMC cancer · 2022Article
- Effects of Sensitized Sorafenib with a Paeoniflorin and Geniposide Mixture on Liver Cancer via the NF-Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma.International journal of molecular sciences · 2021Review
- The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature.International journal of molecular sciences · 2021Review
- Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.International journal of molecular sciences · 2021Review
- Role of hypoxia inducible factor-1 in cancer stem cells (Review).Molecular medicine reports · 2021Review
- Hypoxia-Mediated Complement 1q Binding Protein Regulates Metastasis and Chemoresistance in Triple-Negative Breast Cancer and Modulates the PKC-NF-κB-VCAM-1 Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor-A Literature Review.International journal of molecular sciences · 2020Review
- Postmortem interval determination using mRNA markers and DNA normalization.International journal of legal medicine · 2020Article
- Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression.Biomolecules · 2019Review
- Bladder cancer cells interact with vascular endothelial cells triggering EGFR signals to promote tumor progression.International journal of oncology · 2019Article
- HIF-2α regulates non-canonical glutamine metabolism via activation of PI3K/mTORC2 pathway in human pancreatic ductal adenocarcinoma.Journal of cellular and molecular medicine · 2017Article
- HAF mediates the evasive resistance of anti-angiogenesis TKI through disrupting HIF-1α and HIF-2α balance in renal cell carcinoma.Oncotarget · 2017Article
- miR-186 downregulates protein phosphatase PPM1B in bladder cancer and mediates G1-S phase transition.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Hypoxia-inducible factor as an angiogenic master switch.Frontiers in pediatrics · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is a characteristic feature of solid tumors, leading to malignant behavior. During this process, HIF family members (HIFs) and the NF-κB pathway are activated. In addition, the hypoxia-associated factor (HAF) is reported to participate in the regulation of HIFs. However, the precise relationship among HIFs, HAF and the NF-κB pathway in bladder cancer (BC) remains unknown. In the current investigation, T24 BC cells were exposed to hypoxia, or by plasmid transfection to overexpress HAF or RelA (P65) to demonstrate their roles. The results indicate that hypoxia leads to the elevation of HAF plus activation of the NF-κB pathway, accompanied by the switch of HIF-1α to HIF-2α, resulting in the enhanced ability of malignancy in T24 cells. In order to further demonstrate the significance of this switch, HIF-1α and HIF-2α were co-transfected into T24 cells with HIF-β, respectively. The following results indicate that the T24hif-2α/β cells show enhanced ability of malignancy, accompanied by the maintenance of stem-cell markers, but the T24hif-1α/β cells show higher expression of metabolism-related genes. Boyden assays and wound-healing assays indicate the enhanced ability of malignancy for T24hif-2α/β. Thus, we conclude that on the hypoxic microenvironment, the switching of HIF-1α to HIF-2α, which is driven by HAF through activating the NF-κB pathway, contributes to the malignancy of T24 cells, accompanied by the maintenance of stem-cell markers. This provides us an avenue for understanding the progression of bladder cancer.
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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.