ArticlePloS one2015
Exogenous Restoration of TUSC2 Expression Induces Responsiveness to Erlotinib in Wildtype Epidermal Growth Factor Receptor (EGFR) Lung Cancer Cells through Context Specific Pathways Resulting in Enhanced Therapeutic Efficacy.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 30 citations in OpenAlex.
- From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.Frontiers in immunology · 2024Review
- 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.Communications biology · 2023Article
- Review
- Lipid-based nucleic acid therapeutics with in vivo efficacy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
- Genetic alterations in juvenile cervical clear cell adenocarcinoma unrelated to human papillomavirus.Frontiers in medicine · 2023Article
- NEDD4 degrades TUSC2 to promote glioblastoma progression.Cancer letters · 2022Article
- TUSC2 immunogene enhances efficacy of chemo-immuno combination on KRAS/LKB1 mutant NSCLC in humanized mouse model.Communications biology · 2022Article
- Article
- A Brief Introduction to Current Cancer Gene Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cancer nanotechnology: current status and perspectives.Nano convergence · 2021Review
- The Mechanisms of PD-L1 Regulation in Non-Small-Cell Lung Cancer (NSCLC): Which Are the Involved Players?Cancers · 2020Review
- Article
- Therapeutic implications of fibroblast growth factor receptor inhibitors in a combination regimen for solid tumors.Oncology letters · 2020Review
- The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein.International journal of molecular sciences · 2020Article
- MicroRNA-663 facilitates the growth, migration and invasion of ovarian cancer cell by inhibiting TUSC2.Biological research · 2019Article
- Recent Findings in the Regulation of Programmed Death Ligand 1 Expression.Frontiers in immunology · 2019Review
- TUSC2 Immunogene Therapy Synergizes with Anti-PD-1 through Enhanced Proliferation and Infiltration of Natural Killer Cells in SyngeneicCancer immunology research · 2018Article
- Article
- Tumor suppressor candidate 2 (TUSC2, FUS-1) and human cancers.Discovery medicine · 2017Review
- TUSC2(FUS1)-erlotinib Induced Vulnerabilities in Epidermal Growth Factor Receptor(EGFR) Wildtype Non-small Cell Lung Cancer(NSCLC) Targeted by the Repurposed Drug Auranofin.Scientific reports · 2016Article
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC) cell lines resistant to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.
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