ArticleMolecular cancer research : MCR2022
BRAFV600E-Driven Lung Adenocarcinoma Requires Copper to Sustain Autophagic Signaling and Processing.
Article in Molecular cancer research : MCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Correction: BRAFV600E-Driven Lung Adenocarcinoma Requires Copper to Sustain Autophagic Signaling and Processing.Molecular cancer research : MCR · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Harnessing cuproptosis: a new avenue for targeted cancer therapies.Apoptosis : an international journal on programmed cell death · 2025Review
- Recent advances in copper sulfide nanoparticles for cancer diagnosis and therapy.Materials today. Bio · 2025Review
- An Alkyne-Directed Cleavage Approach for Activity-Based Cu(I) Sensing Reveals Manganese-Promoted Sensitization of Cuproptosis.Journal of the American Chemical Society · 2025Article
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system.Cancer pathogenesis and therapy · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Roles of Copper Transport Systems Members in Breast Cancer.Cancer medicine · 2024Review
- GLUT1 inhibitor BAY-876 induces apoptosis and enhances anti-cancer effects of bitter receptor agonists in head and neck squamous carcinoma cells.Cell death discovery · 2024Article
- Cuproptosis in cancer: biological implications and therapeutic opportunities.Cellular & molecular biology letters · 2024Review
- Cuproptosis: unveiling a new frontier in cancer biology and therapeutics.Cell communication and signaling : CCS · 2024Review
- IAPP blocks anti-breast cancer function of CD8Frontiers in immunology · 2024Article
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- Cuproptosis: mechanisms and links with cancers.Molecular cancer · 2023Review
- Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies.Frontiers in pharmacology · 2023Review
- Copper-Dependent Kinases and Their Role in Cancer Inception, Progression and Metastasis.Biomolecules · 2022Review
- Identification of cuprotosis-mediated subtypes, the development of a prognosis model, and influence immune microenvironment in hepatocellular carcinoma.Frontiers in oncology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
The transition metal copper (Cu) is an essential micronutrient required for development and proliferation, but the molecular mechanisms by which Cu contributes to these processes is not fully understood. Although traditionally studied as a static cofactor critical for the function of Cu-dependent enzymes, an expanding role for Cu is emerging to include its novel function as a dynamic mediator of signaling processes through the direct control of protein kinase activity. We now appreciate that Cu directly binds to and influences MEK1/2 and ULK1/2 kinase activity, and show here that reductions in MAPK and autophagic signaling are associated with dampened growth and survival of oncogenic BRAF-driven lung adenocarcinoma cells upon loss of Ctr1. Efficient autophagy, clonogenic survival, and tumorigenesis of BRAF-mutant cells required ULK1 Cu-binding. Although treatment with canonical MAPK inhibitors resulted in the upregulation of protective autophagy, mechanistically, the Cu chelator tetrathiomolybdate (TTM) was sufficient to target both autophagic and MAPK signaling as a means to blunt BRAF-driven tumorigenic properties. These findings support leveraging Cu chelation with TTM as an alternative therapeutic strategy to impair autophagy and MAPK signaling. As traditional MAPK monotherapies initiate autophagy signaling and promote cancer cell survival. IMPLICATIONS: We establish that copper chelation therapy inhibits both autophagy and MAPK signaling in BRAFV600E-driven lung adenocarcinoma, thus overcoming the upregulation of protective autophagy elicited by canonical MAPK pathway inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.