ArticleProceedings of the National Academy of Sciences of the United States of America1999
Mechanism of biological synergy between cellular Src and epidermal growth factor receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 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.
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
188 citing papers in PubMed, 463 citations in OpenAlex.
- Phase II trial of dasatinib for patients with acquired resistance to treatment with the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib or gefitinib.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2011Trial
- Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non-small-cell lung cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Trial
- Rosmarinic acid inhibits norepinephrine-induced metastatic capacity of triple negative breast cancer cells by Src kinase inactivation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells.Cell and tissue research · 2026Article
- Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap.Nature chemical biology · 2026Article
- Dioxins do not only bind to AHR but also team up with EGFR at the cell-surface: a novel mode of action of toxicological relevance?EXCLI journal · 2025Review
- Transactivation of the EGF receptor as a novel desensitization mechanism for G protein-coupled receptors, illustrated by dopamine D2-like and βCellular & molecular biology letters · 2024Article
- The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis.Nature communications · 2024Article
- Targeting endocytosis to sensitize cancer cells to programmed cell death.Biochemical Society transactions · 2024Review
- EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.Neuro-oncology · 2024Article
- YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer.Archives of toxicology · 2024Article
- EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling.Science advances · 2024Article
- The Chemical Inhibitors of Endocytosis: From Mechanisms to Potential Clinical Applications.Cells · 2023Review
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Dual clathrin and integrin signaling systems regulate growth factor receptor activation.Nature communications · 2022Article
- Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma.Open life sciences · 2022Article
- The Androgen Receptor and Its Crosstalk With the Src Kinase During Castrate-Resistant Prostate Cancer Progression.Frontiers in oncology · 2022Review
- Article
- New Structural Perspectives in G Protein-Coupled Receptor-Mediated Src Family Kinase Activation.International journal of molecular sciences · 2021Review
- Standard of Care and Promising New Agents for the Treatment of Mesenchymal Triple-Negative Breast Cancer.Cancers · 2021Review
128 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of both cellular Src (c-Src) and the epidermal growth factor receptor (EGFR) occurs in many of the same human tumors, suggesting that they may functionally interact and contribute to the progression of cancer. Indeed, in murine fibroblasts, overexpression of c-Src has been shown to potentiate the mitogenic and tumorigenic capacity of the overexpressed EGFR. Potentiation correlated with the ability of c-Src to physically associate with the activated EGFR and the appearance of two unique in vivo phosphorylations on the receptor (Tyr-845 and Tyr-1101). Using stable cell lines of C3H10T1/2 murine fibroblasts that contain kinase-deficient (K-) c-Src and overexpressed wild-type EGFR, we show that the kinase activity of c-Src is required for both the biological synergy with the receptor and the phosphorylations on the receptor, but not for the association of c-Src with the receptor. In transient transfection assays, not only epidermal growth factor but also serum- and lysophosphatidic acid-induced DNA synthesis was ablated in a dominant-negative fashion by a Y845F mutant of the EGFR, indicating that c-Src-induced phosphorylation of Y845 is critical for the mitogenic response to both the EGFR and a G protein-coupled receptor (lysophosphatidic acid receptor). Unexpectedly, the Y845F mutant EGFR was found to retain its full kinase activity and its ability to activate the adapter protein SHC and extracellular signal-regulated kinase ERK2 in response to EGF, demonstrating that the mitogenic pathway involving phosphorylation of Y845 is independent of ERK2-activation. The application of these findings to the development of novel therapeutics for human cancers that overexpress c-Src and EGFR is discussed.
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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.