ArticleNature cell biology2016
The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer.
Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 317 papers.
What it found
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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
317 citing papers in PubMed, 568 citations in OpenAlex.
- High expression of long non-coding RNA Linc-A associates with poor survival in patients with colorectal cancer.Molecular biology reports · 2020Trial
- The hidden players: LncRNA-Encoded micropeptides in cancer hallmarks.Cellular and molecular life sciences : CMLS · 2026Review
- Focusing on toxicity management: Challenges and strategies for HER2-targeted antibody-drug conjugates in breast cancer.Breast (Edinburgh, Scotland) · 2026Review
- The loss of glycoprotein nonmetastatic melanoma protein B (GPNMB) alters endothelial cell permeability, metabolism, and survival during infectious challenge.Clinical science (London, England : 1979) · 2026Article
- Exploring the Role of Long Noncoding RNAs in Breast Cancer Progression: A Comprehensive Study on Biomarkers and Therapeutic Approaches.Cancer medicine · 2026Review
- Identification of AC025811.3 and AC012354.6 as two critical survival-related lncRNAs for uterine corpus cancer.PloS one · 2026Article
- Computational discovery of conserved RNA structures and functional characterization of a structured lncRNA inNon-coding RNA research · 2025Article
- Metabolomics as a tool for understanding and treating triple-negative breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- Exploring the role of HIF-1α in pathogenesis of parkinson's disease and its potential as a therapeutic target.Molecular biology reports · 2025Review
- GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation.EMBO reports · 2025Article
- LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology.Functional & integrative genomics · 2025Review
- Prognostic value of a lncRNA signature in early-stage invasive breast cancer patients.Cancer cell international · 2025Article
- Exploring the roles and clinical potential of exosome-derived non-coding RNAs in glioma.IBRO neuroscience reports · 2025Review
- The Role of Long Non-Coding RNAs in Modulating the Immune Microenvironment of Triple-Negative Breast Cancer: Mechanistic Insights and Therapeutic Potential.Biomolecules · 2025Review
- Role of exercise on the reduction of cancer development: a mechanistic review from the lncRNA point of view.Clinical and experimental medicine · 2025Review
- Exosomal Lipids in Cancer Progression and Metastasis.Cancer medicine · 2025Review
- GPNMB is a novel binding partner of FGFR1 that affects tumorigenic potential through AKT phosphorylation in TNBC.Cancer science · 2025Article
- Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors.Nature chemical biology · 2025Article
- Involvement of lncRNA in cancer diagnosis and prognosis and clinical implications.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2025Review
257 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Although long non-coding RNAs (lncRNAs) predominately reside in the nucleus and exert their functions in many biological processes, their potential involvement in cytoplasmic signal transduction remains unexplored. Here, we identify a cytoplasmic lncRNA, LINK-A (long intergenic non-coding RNA for kinase activation), which mediates HB-EGF-triggered, EGFR:GPNMB heterodimer-dependent HIF1α phosphorylation at Tyr 565 and Ser 797 by BRK and LRRK2, respectively. These events cause HIF1α stabilization, HIF1α-p300 interaction, and activation of HIF1α transcriptional programs under normoxic conditions. Mechanistically, LINK-A facilitates the recruitment of BRK to the EGFR:GPNMB complex and BRK kinase activation. The BRK-dependent HIF1α Tyr 565 phosphorylation interferes with Pro 564 hydroxylation, leading to normoxic HIF1α stabilization. Both LINK-A expression and LINK-A-dependent signalling pathway activation correlate with triple-negative breast cancer (TNBC), promoting breast cancer glycolysis reprogramming and tumorigenesis. Our findings illustrate the magnitude and diversity of cytoplasmic lncRNAs in signal transduction and highlight the important roles of lncRNAs in cancer.
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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.