ArticleOncogene2016
Smad4 loss promotes lung cancer formation but increases sensitivity to DNA topoisomerase inhibitors.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 46 citations in OpenAlex.
- Association of SMAD4 gene polymorphisms with human papillomavirus infection and risk of cervical cancer: a case-control study.BMC cancer · 2026Article
- MicroRNA-mediated changes contributing to benzo[a]pyrene toxicity in a 3D respiratory model for asthma.Current research in toxicology · 2026Article
- Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response.Nature reviews. Cancer · 2025Review
- HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Single Circulating-Tumor-Cell-Targeted Sequencing to Identify Somatic Variants in Liquid Biopsies in Non-Small-Cell Lung Cancer Patients.Current issues in molecular biology · 2022Article
- Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma.NPJ precision oncology · 2021Article
- Correlation between loss of Smad4 and clinical parameters of non-small cell lung cancer: an observational cohort study.BMC pulmonary medicine · 2021Observational
- [Clinical Value of Cerebrospinal Fluid ctDNA in Patients with Non-small Cell Lung Cancer Meningeal Metastasis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Article
- SMAD-6, -7 and -9 are potential molecular biomarkers for the prognosis in human lung cancer.Oncology letters · 2020Article
- Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates.Cells · 2020Review
- Targeting RICTOR Sensitizes SMAD4-Negative Colon Cancer to Irinotecan.Molecular cancer research : MCR · 2020Article
- Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer.Journal of oncology · 2020Article
- Development of syngeneic murine cell lines for use in immunocompetent orthotopic lung cancer models.Cancer cell international · 2020Article
- Lessons learned from SMAD4 loss in squamous cell carcinomas.Molecular carcinogenesis · 2019Review
- Inter- and intra-tumor heterogeneity of SMAD4 loss in head and neck squamous cell carcinomas.Molecular carcinogenesis · 2019Article
- Article
- deepDriver: Predicting Cancer Driver Genes Based on Somatic Mutations Using Deep Convolutional Neural Networks.Frontiers in genetics · 2019Article
- Article
- miR‑3147 serves as an oncomiR in vulvar squamous cell cancer via Smad4 suppression.Molecular medicine reports · 2018Article
- The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma.Journal of pathology and translational medicine · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Non-small-cell lung cancer (NSCLC) is a common malignancy with a poor prognosis. Despite progress targeting oncogenic drivers, there are no therapies targeting tumor-suppressor loss. Smad4 is an established tumor suppressor in pancreatic and colon cancer; however, the consequences of Smad4 loss in lung cancer are largely unknown. We evaluated Smad4 expression in human NSCLC samples and examined Smad4 alterations in large NSCLC data sets and found that reduced Smad4 expression is common in human NSCLC and occurs through a variety of mechanisms, including mutation, homozygous deletion and heterozygous loss. We modeled Smad4 loss in lung cancer by deleting Smad4 in airway epithelial cells and found that Smad4 deletion both initiates and promotes lung tumor development. Interestingly, both Smad4(-/-) mouse tumors and human NSCLC samples with reduced Smad4 expression demonstrated increased DNA damage, whereas Smad4 knockdown in lung cancer cells reduced DNA repair and increased apoptosis after DNA damage. In addition, Smad4-deficient NSCLC cells demonstrated increased sensitivity to both chemotherapeutics that inhibit DNA topoisomerase and drugs that block double-strand DNA break repair by non-homologous end joining. In sum, these studies establish Smad4 as a lung tumor suppressor and suggest that the defective DNA repair phenotype of Smad4-deficient tumors can be exploited by specific therapeutic strategies.
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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.