Trial reportThe Journal of clinical investigation2014
LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 40 citations in OpenAlex.
- GATRSyn: Advancing Anticancer Drug Synergy Prediction Through Graph Attention Networks and Transformer-based Feature Re-embedding.Interdisciplinary sciences, computational life sciences · 2026Article
- Dynamic methylation and expression of alternative promoters for oestrogen receptor alpha in cell line models of fulvestrant resistance.Molecular oncology · 2025Article
- Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer.Journal of the Endocrine Society · 2023Article
- Src heterodimerically activates Lyn or Fyn to serve as targets for the diagnosis and treatment of esophageal squamous cell carcinoma.Science China. Life sciences · 2023Article
- Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients.Renal failure · 2023Article
- Review
- The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer.Journal of personalized medicine · 2021Review
- The Src-family Kinase Lyn in Immunoreceptor Signaling.Endocrinology · 2021Review
- Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition.Cell communication and signaling : CCS · 2021Review
- High-ThroughputFrontiers in oncology · 2021Article
- Comprehensively investigating the expression levels and the prognostic role of transforming growth factor beta-induced (TGFBI) in glioblastoma multiforme.Translational cancer research · 2020Article
- The role of deubiquitinating enzymes in cancer drug resistance.Cancer chemotherapy and pharmacology · 2020Review
- Article
- Dehydroepiandrosterone Induces Temozolomide Resistance Through Modulating Phosphorylation and Acetylation of Sp1 in Glioblastoma.Molecular neurobiology · 2019Article
- Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells.Cell reports · 2018Article
- Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Distal CpG islands can serve as alternative promoters to transcribe genes with silenced proximal promoters.Genome research · 2017Article
- BIRC6 mediates imatinib resistance independently of Mcl-1.PloS one · 2017Article
- WP1130 increases cisplatin sensitivity through inhibition ofAmerican journal of translational research · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Estrogen receptor-positive (ER(+)) breast cancers adapt to hormone deprivation and become resistant to antiestrogen therapy. Here, we performed deep sequencing on ER(+) tumors that remained highly proliferative after treatment with the aromatase inhibitor letrozole and identified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN. Evaluation of 463 breast tumors in The Cancer Genome Atlas revealed four LYN mutations, two of which affected the SH2 domain. In addition, LYN was upregulated in multiple ER(+) breast cancer lines resistant to long-term estrogen deprivation (LTED). An RNAi-based kinome screen revealed that LYN is required for growth of ER(+) LTED breast cancer cells. Kinase assays and immunoblot analyses of SRC substrates in transfected cells indicated that LYN(D189Y) has higher catalytic activity than WT protein. Further, LYN(D189Y) exhibited reduced phosphorylation at the inhibitory Y507 site compared with LYN(WT). Other SH2 domain LYN mutants, E159K and K209N, also exhibited higher catalytic activity and reduced inhibitory site phosphorylation. LYN(D189Y) overexpression abrogated growth inhibition by fulvestrant and/or the PI3K inhibitor BKM120 in 3 ER(+) breast cancer cell lines. The SFK inhibitor dasatinib enhanced the antitumor effect of BKM120 and fulvestrant against estrogen-deprived ER(+) xenografts but not LYN(D189Y)-expressing xenografts. These results suggest that LYN mutations mediate escape from antiestrogens in a subset of ER(+) breast cancers.
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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 Socratic graph.