Asset Details
Do you wish to reserve the book?
Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway
Do you wish to request the book?
Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway
2025
Overview
The MET exon 14 skipping mutation (named METex14Del) described in lung cancer leads to prolonged activation of signaling pathways and aberrant cell responses, but the link between HGF signaling and cell responses remains unclear. A putative lung cancer regulatory network of influential transcription factors was constructed from the transcriptomes of lung cancer cell lines. Transcriptomic data from METex14Del-expressing cells, stimulated or not by HGF, were mapped onto this lung cancer reference network and revealed activation of a major regulatory node composed mainly by the highly influential transcription factors ETS1, FOSL1 and SMAD3. HGF activation of METex14Del receptor induced the expression and phosphorylation of these three master regulators and the expression of their predicted target genes involved in migration and invasion. All these molecular and biological effects were inhibited by trametinib, a MEK inhibitor, which was potentiated by combination with capmatinib, a MET inhibitor. New mapping with transcriptomic data from trametinib-treated METex14Del cells validated the key role of the RAS-ERK pathway signaling in the activation of ETS1, FOSL1 and SMAD3 regulators and the induction of their target genes in HGF-activated METex14Del receptor. Thus, we report an original and powerful strategy to uncover key regulators, including transcription factors that have not been widely described in METex14Del signaling, such as SMAD3. These factors are activated by specific signaling pathways and could provide a novel therapeutic strategy involving a combination of receptor and signaling inhibitors.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/95
/ 14/56
/ 38
/ 38/1
/ 38/61
/ 38/77
/ 42
/ 45
/ 59
/ 82/29
/ 82/80
/ 96/95
/ Biomedical and Life Sciences
/ Cell Movement - drug effects
/ Gene Expression Regulation, Neoplastic - drug effects
/ Hepatocyte Growth Factor - metabolism
/ Hepatocyte Growth Factor - pharmacology
/ Humans
/ Kinases
/ Ligands
/ MAP Kinase Signaling System - drug effects
/ MAP Kinase Signaling System - genetics
/ Mutation
/ Proteins
/ Proto-Oncogene Protein c-ets-1 - genetics
/ Proto-Oncogene Protein c-ets-1 - metabolism
/ Proto-Oncogene Proteins c-fos - genetics
/ Proto-Oncogene Proteins c-fos - metabolism
/ Proto-Oncogene Proteins c-met - genetics
/ Proto-Oncogene Proteins c-met - metabolism
/ Pyrimidinones - pharmacology
/ Tumors
