ArticlePLoS biology2020
NRF2 negatively regulates primary ciliogenesis and hedgehog signaling.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 26 citations in OpenAlex.
- Multifaceted role of primary cilia and ciliary proteins: A potential nexus for hedgehog signaling and prostate cancer.Biochimica et biophysica acta. Molecular basis of disease · 2026Review
- Article
- Deciphering vesicle-assisted transport mechanisms in cytoplasm to cilium trafficking.Frontiers in cellular neuroscience · 2024Review
- Oxidative Stress Induces Skin Pigmentation in Melasma by Inhibiting Hedgehog Signaling.Antioxidants (Basel, Switzerland) · 2023Article
- Oncogenic and immunological values of RBM34 in osteosarcoma and its pan-cancer analysis.American journal of cancer research · 2023Article
- Spatial Analysis of NQO1 in Non-Small Cell Lung Cancer Shows Its Expression Is Independent of NRF1 and NRF2 in the Tumor Microenvironment.Biomolecules · 2022Article
- Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer.Cancer research · 2022Article
- Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- STAT6/VDR Axis Mitigates Lung Inflammatory Injury by Promoting Nrf2 Signaling Pathway.Oxidative medicine and cellular longevity · 2022Article
- Keap1/Nrf2 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- BBS Proteins Affect Ciliogenesis and Are Essential for Hedgehog Signaling, but Not for Formation of iPSC-Derived RPE-65 Expressing RPE-Like Cells.International journal of molecular sciences · 2021Article
- Nrf2-A Molecular Target for Sepsis Patients in Critical Care.Biomolecules · 2020Review
- NRF2 and the Ambiguous Consequences of Its Activation during Initiation and the Subsequent Stages of Tumourigenesis.Cancers · 2020Review
- NRF2 and Primary Cilia: An Emerging Partnership.Antioxidants (Basel, Switzerland) · 2020Review
- Bixin Protects Against Kidney Interstitial Fibrosis Through Promoting STAT6 Degradation.Frontiers in cell and developmental biology · 2020Article
- Kinesin family member 3A induces related diseases via wingless-related integration site/β-catenin signaling pathway.Science progressReview
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Primary cilia are lost during cancer development, but the mechanism regulating cilia degeneration is not determined. While transcription factor nuclear factor-erythroid 2-like 2 (NRF2) protects cells from oxidative, proteotoxic, and metabolic stress in normal cells, hyperactivation of NRF2 is oncogenic, although the detailed molecular mechanisms by which uncontrolled NRF2 activation promotes cancer progression remain unclear. Here, we report that NRF2 suppresses hedgehog (Hh) signaling through Patched 1 (PTCH1) and primary ciliogenesis via p62/sequestosome 1 (SQSTM1). PTCH1, a negative regulator of Hh signaling, is an NRF2 target gene, and as such, hyperactivation of NRF2 impairs Hh signaling. NRF2 also suppresses primary cilia formation through p62-dependent inclusion body formation and blockage of Bardet-Biedl syndrome 4 (BBS4) entrance into cilia. Simultaneous ablation of PTCH1 and p62 completely abolishes NRF2-mediated inhibition of both primary ciliogenesis and Hh signaling. Our findings reveal a previously unidentified role of NRF2 in controlling a cellular organelle, the primary cilium, and its associated Hh signaling pathway and also uncover a mechanism by which NRF2 hyperactivation promotes tumor progression via primary cilia degeneration and aberrant Hh signaling. A better understanding of the crosstalk between NRF2 and primary cilia/Hh signaling could not only open new avenues for cancer therapeutic discovery but could also have significant implications regarding pathologies other than cancer, including developmental disorders, in which improper primary ciliogenesis and Hh signaling play a major role.
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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.