دورية أكاديمية
A Reversible Shift of Driver Dependence from EGFR to Notch1 in Non-Small Cell Lung Cancer as a Cause of Resistance to Tyrosine Kinase Inhibitors
| العنوان: | A Reversible Shift of Driver Dependence from EGFR to Notch1 in Non-Small Cell Lung Cancer as a Cause of Resistance to Tyrosine Kinase Inhibitors |
|---|---|
| المؤلفون: | Francesca Iommelli, Viviana De Rosa, Cristina Terlizzi, Rosa Fonti, Rosa Camerlingo, Maria Patrizia Stoppelli, C. Allison Stewart, Lauren Averett Byers, David Piwnica-Worms, Silvana Del Vecchio |
| المصدر: | Cancers, Vol 13, Iss 9, p 2022 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Notch1, EGFR, EMT, tumor spheres, NSCLC, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Notch1 plays a key role in epithelial-mesenchymal transition (EMT) and in the maintenance of cancer stem cells. In the present study we tested whether high levels of activated Notch1 in oncogene-driven NSCLC can induce a reversible shift of driver dependence from EGFR to Notch1, and thus causing resistance to EGFR inhibitors. Adherent cells (parental) and tumor spheres (TS) from NSCLC H1975 cells and patient-derived CD133-positive cells were tested for EGFR and Notch1 signaling cascade. The Notch1-dependent modulation of EGFR, NCID, Hes1, p53, and Sp1 were then analyzed in parental cells by binding assays with a Notch1 agonist, DLL4. TS were more resistant than parental cells to EGFR inhibitors. A strong upregulation of Notch1 and a concomitant downregulation of EGFR were observed in TS compared to parental cells. Parental cell exposure to DLL4 showed a dose-dependent decrease of EGFR and a simultaneous increase of NCID, Hes1, p53, and Sp1, along with the dislocation of Sp1 from the EGFR promoter. Furthermore, an enhanced interaction between p53 and Sp1 was observed in TS. In NSCLC cells, high levels of active Notch1 can promote a reversible shift of driver dependence from EGFR to Notch1, leading to resistance to EGFR inhibitors. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 13092022 2072-6694 |
| العلاقة: | https://www.mdpi.com/2072-6694/13/9/2022Test; https://doaj.org/toc/2072-6694Test |
| DOI: | 10.3390/cancers13092022 |
| الوصول الحر: | https://doaj.org/article/d699f348411d4119a93d9529f216e920Test |
| رقم الانضمام: | edsdoj.699f348411d4119a93d9529f216e920 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 13092022 20726694 |
|---|---|
| DOI: | 10.3390/cancers13092022 |