ArticleOncotarget2017
EGFR mediates activation of RET in lung adenocarcinoma with neuroendocrine differentiation characterized by ASCL1 expression.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Unveiling prognostic factors and predictive modeling in lung adenocarcinoma with neuroendocrine differentiation.Translational cancer research · 2025Article
- The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.Frontiers in oncology · 2025Review
- RET overexpression leads to increased brain metastatic competency in luminal breast cancer.Journal of the National Cancer Institute · 2024Article
- ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.Cancer research · 2024Article
- Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia.Cancer science · 2024Article
- Identification of signaling pathways associated with achaete-scute homolog 1 in glioblastomas through ChIP-seq data bioinformatics.Frontiers in genetics · 2022Article
- Review
- Loss of cellular identity in common pre-clinical models of serine‑threonine kinase 11 (Liver kinase B1) loss.Cancer treatment and research communications · 2021Article
- RET isoforms contribute differentially to invasive processes in pancreatic ductal adenocarcinoma.Oncogene · 2020Article
- Article
- GGA3-mediated recycling of the RET receptor tyrosine kinase contributes to cell migration and invasion.Oncogene · 2020Article
- A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.Human pathology · 2019Article
- Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations.Journal of personalized medicine · 2018Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Achaete-scute homolog 1 (ASCL1) is a neuroendocrine transcription factor specifically expressed in 10-20% of lung adenocarcinomas (AD) with neuroendocrine (NE) differentiation (NED). ASCL1 functions as an upstream regulator of the RET oncogene in AD with high ASCL1 expression (A+AD). RET is a receptor tyrosine kinase with two main human isoforms; RET9 (short) and RET51 (long). We found that elevated expression of RET51 associated mRNA was highly predictive of poor survival in stage-1 A+AD (p=0.0057). Functional studies highlighted the role of RET in promoting invasive properties of A+AD cells. Further, A+AD cells demonstrated close to 10 fold more sensitivity to epidermal growth factor receptor (EGFR) inhibitors, including gefitinib, than AD cells with low ASCL1 expression. Treatment with EGF robustly induced phosphorylation of RET at Tyr-905 in A+AD cells with wild type EGFR. This phosphorylation was blocked by gefitinib and by siRNA-EGFR. Immunoprecipitation experiments found EGFR in a complex with RET in the presence of EGF and suggested that RET51 was the predominant RET isoform in the complex. In the microarray datasets of stage-1 and all stages of A+AD, high levels of EGFR and RET RNA were significantly associated with poor overall survival (p < 0.01 in both analyses). These results implicate EGFR as a key regulator of RET activation in A+AD and suggest that EGFR inhibitors may be therapeutic in patients with A+AD tumors even in the absence of an EGFR or RET mutation.
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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.