| Added by | amaraver |
|---|---|
| Last modified by | standudu |
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | Therapeutic effect of ?-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK |
| Creator | Maraver et al. |
| Author | Antonio Maraver |
| Author | Pablo J. Fernández-Marcos |
| Author | Daniel Herranz |
| Author | Maribel Muñoz-Martin |
| Author | Gonzalo Gomez-Lopez |
| Author | Marta Cañamero |
| Author | Francisca Mulero |
| Author | Diego Megías |
| Author | Marta Sanchez-Carbayo |
| Author | Jie Shen |
| Author | Montserrat Sanchez-Cespedes |
| Author | Teresa Palomero |
| Author | Adolfo Ferrando |
| Author | Manuel Serrano |
| Abstract | Here, we have investigated the role of the Notch pathway in the generation and maintenance of Kras(G12V)-driven non-small cell lung carcinomas (NSCLCs). We demonstrate by genetic means that ?-secretase and RBPJ are essential for the formation of NSCLCs. Of importance, pharmacologic treatment of mice carrying autochthonous NSCLCs with a ?-secretase inhibitor (GSI) blocks cancer growth. Treated carcinomas present reduced HES1 levels and reduced phosphorylated ERK without changes in phosphorylated MEK. Mechanistically, we show that HES1 directly binds to and represses the promoter of DUSP1, encoding a dual phosphatase that is active against phospho-ERK. Accordingly, GSI treatment upregulates DUSP1 and decreases phospho-ERK. These data provide proof of the in vivo therapeutic potential of GSIs in primary NSCLCs. |
| Publication | Cancer Cell |
| Volume | 22 |
| Issue | 2 |
| Pages | 222-234 |
| Date | Aug 14, 2012 |
| Journal Abbr | Cancer Cell |
| Language | eng |
| DOI | 10.1016/j.ccr.2012.06.014 |
| ISSN | 1878-3686 |
| Library Catalog | PubMed |
| Extra | 00102 PMID: 22897852 PMCID: PMC3813920 |
| Tags | Amyloid Precursor Protein Secretases, Animals, Basic Helix-Loop-Helix Transcription Factors, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Dual Specificity Phosphatase 1, Enzyme Inhibitors, Extracellular Signal-Regulated MAP Kinases, Homeodomain Proteins, Humans, Lung Neoplasms, Mice, Mutant Proteins, Phosphorylation, Presenilin-1, Presenilin-2, Prognosis, Promoter Regions, Genetic, Protein Binding, ras Proteins, Receptors, Notch, Repressor Proteins, Signal Transduction, top, Transcription Factor HES-1, Treatment Outcome |
| Date Added | 2020/01/23 - 10:38:15 |
| Date Modified | 2020/02/16 - 18:36:58 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
