ArticleOncogene2019
The oncoprotein HBXIP competitively binds KEAP1 to activate NRF2 and enhance breast cancer cell growth and metastasis.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- In vivo CRISPR screening identifies metastasis suppressors in triple-negative breast cancer.Nature communications · 2026Article
- Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.Drug design, development and therapy · 2026Review
- Attack cancer: Through autophagic modulations as suppressor or promoter.World journal of clinical oncology · 2025Review
- Genetic evidence for causal effects of inflammatory protein factors on breast cancer.Discover oncology · 2025Article
- Increased expression ofTranslational cancer research · 2024Article
- Engineered Cas9 variants bypass Keap1-mediated degradation in human cells and enhance epigenome editing efficiency.Nucleic acids research · 2024Article
- Research progress on oncoprotein hepatitis B X‑interacting protein (Review).Molecular medicine reports · 2024Review
- Antioxidant curcumin induces oxidative stress to kill tumor cells (Review).Oncology letters · 2024Review
- Emerging Role of Ferroptosis in Breast Cancer: Characteristics, Therapy, and Translational Implications for the Present and Future.Current molecular medicine · 2024Review
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
- Autophagy and autophagy-related pathways in cancer.Nature reviews. Molecular cell biology · 2023Review
- Nanoparticle-Based Antioxidants in Stress Signaling and Programmed Cell Death in Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2023Review
- The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis.Molecules and cells · 2023Review
- Involvement of redox signalling in tumour cell dormancy and metastasis.Cancer metastasis reviews · 2023Review
- Nrf2/Keap1/ARE signaling: Towards specific regulation.Life sciences · 2022Review
- HBXIP induces anoikis resistance by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis and stabilize Prdx1 in breast cancer.NPJ breast cancer · 2022Article
- Circular RNA circCCDC85A inhibits breast cancer progression via acting as a miR-550a-5p sponge to enhance MOB1A expression.Breast cancer research : BCR · 2022Article
- Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma.International journal of molecular sciences · 2021Review
- Involvement of NRF2 in Breast Cancer and Possible Therapeutical Role of Polyphenols and Melatonin.Molecules (Basel, Switzerland) · 2021Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear factor E2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling cascades is a key transcriptional pathway governing cellular oxidative stress and tumor development. Mammalian hepatitis B X-interacting protein (HBXIP) has critical roles in modulating cancer malignance and tumor progression. However, whether HBXIP interacts with KEAP1 and NRF2 is unclear. Here, we found that HBXIP can effectually compete with NRF2 for binding with KEAP1 protein via its highly conserved GLNLG motif. The HBXIP-mediated reduction in NRF2-KEAP1 complexes promotes NRF2 accumulation and nuclear entry, which facilities the activation of antioxidant response element (ARE)-dependent signaling cascades, thereby reducing the accumulation of endogenous cellular reactive oxygen species (ROS). We also found a strong positive correlation between HBXIP expression and NRF2 expression in breast cancer cells, tissue microarrays and clinical breast cancer tissues. Furthermore, this positive correlation was further confirmed via analysis of 1905 clinical cases of breast carcinoma provided by the cancer genomics database cBioPortal. Strikingly, disrupting the HBXIP-KEAP1 axis via mutating the GLNLG motif of HBXIP leads to potent inhibition of the malignancy of breast carcinoma both in vivo and in vitro. Our findings broaden our understanding of HBXIP as a modulation factor of cellular oxidative stress and address a novel regulatory mechanism governing redox homeostasis and the progression of breast carcinoma.
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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.