ArticleCancers2021
p62-Induced Cancer-Associated Fibroblast Activation via the Nrf2-ATF6 Pathway Promotes Lung Tumorigenesis.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 97 citations in OpenAlex.
- Dual Roles of Autophagy in Endometrial Fibrosis and Its Implications in Age-Related Reproductive Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Aquaporin 5 and Nuclear Factor Erythroid 2-Related Factor 2 Upregulation in Tumor and Stroma Is Associated with Poor Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Article
- Multi-omics analysis identifies a major histocompatibility complex class II-associated antigen-presenting cancer-associated fibroblast-like state linked to the nuclear factor erythroid 2-related factor 2-karyopherin subunit beta 1 axis in nonsmall cell lung cancer.Journal of cell communication and signaling · 2026Article
- The pro-cancer and immunosuppressive activity of macrophage-transformed cancer-associated fibroblasts in oral squamous cell carcinoma.Journal of advanced research · 2026Article
- Deactivation of CK1α enhances the anti-cancer effects of salinomycin in colorectal cancer HCT116 cells.Biochemistry and biophysics reports · 2025Article
- Autophagic degradation of SQSTM1 enables fibroblast activation to accelerate wound healing.Autophagy · 2025Article
- Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Hidden forces: the impact of cancer-associated fibroblasts on non-small cell lung cancer development and therapy.Journal of translational medicine · 2025Review
- Sphingosine 1-phosphate derived from tumor-educated hepatic stellate cells combining with S1PR4 promotes tumor associated macrophages differentiation through FAO modulation.Scientific reports · 2025Article
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- DERL3 exacerbates glioblastoma malignancy through endoplasmic reticulum stress-dependent mechanisms.American journal of cancer research · 2025Article
- Targeting Epigenetic Alterations Linked to Cancer-Associated Fibroblast Phenotypes in Lung Cancer.Cancers · 2024Article
- Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum.Nature communications · 2024Article
- Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution.Journal of hematology & oncology · 2024Review
- Asperuloside inhibits the activation of pancreatic cancer-associated fibroblasts via activating transcription factor 6.Discover oncology · 2024Article
- FGFR2-triggered autophagy and activation of Nrf-2 reduce breast cancer cell response to anti-ER drugs.Cellular & molecular biology letters · 2024Article
- PERP May Affect the Prognosis of Lung Adenocarcinoma by Inhibiting Apoptosis.Cancer management and research · 2024Article
- Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials.Molecular cancer · 2023Review
- Exo-miR-1290-induced by COX-2 overexpression promotes cancer-associated fibroblasts activation and tumor progression by CUL3-Nrf2 pathway in lung adenocarcinoma.Cell communication and signaling : CCS · 2023Article
- PPM1H is down-regulated by ATF6 and dephosphorylates p-RPS6KB1 to inhibit progression of hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) are important in tumor progression. The autophagy adaptor protein, p62/SQSTM1/Sequestosome-1, is up-regulated in tumors, but down-regulated in CAFs in the early stages of lung adenocarcinoma. We investigated whether p62-induced autophagy might control CAF activation. Under CAF-inducing conditions, like hypoxia or cancer cell co-cultures, p62 ablation or autophagy inhibition with hydroxychloroquine (HCQ) impaired CAF activation and reduced transforming growth factor beta (TGFβ) production, which impeded tumor growth. During CAF activation, p62-induced autophagy up-regulated the expression of the anti-oxidant signaling protein, nuclear factor erythroid 2-related factor 2 (Nrf2), and the ER-stress response regulator, activating transcription factor 6 (ATF6). Genetically or pharmacologically inhibiting the Nrf2-ATF6 pathway totally blocked CAF activation and tumor progression. These results demonstrate that p62 is a key modulator of primary lung adenocarcinoma progression. Thus, targeting the p62-Nrf2 autophagy signaling pathway might be a novel, stroma-focused, cancer prevention and/or treatment strategy.
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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.