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| Status |
Public on May 27, 2022 |
| Title |
MET∆14 promotes a ligand-dependent, AKT-driven invasive growth |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
MET is an oncogene encoding the tyrosine kinase receptor for hepatocyte growth factor (HGF). Upon ligand binding, MET activates multiple signal transducers, including PI3K/AKT (survival/migration), STAT3 (differentiation), and MAPK (proliferation). When mutated or amplified, MET becomes a "driver" for the onset and progression of cancer. The most frequent mutations in the MET gene affect the splicing sites of exon 14, leading to its "skipping" from mRNA and consequent deletion of the receptor's juxtamembrane domain (MET∆14). It is currently believed that, as in gene amplification, MET∆14 kinase is constitutively active. Analysis of MET in carcinoma cell lines showed that MET∆14 strictly depends on HGF for kinase activation. Compared to WT MET, ∆14 is sensitive to lower HGF concentrations, with more sustained kinase response, ultimately leading to a robust phosphorylation of AKT, without affecting MAPK or STAT3. This altered kinase response leads to a distinctive transcriptomic signature. Functional studies revealed that ∆14 activation is predominantly responsible for enhanced protection from apoptosis and cellular migration. Thus, the unique HGF-dependent ∆14 oncogenic activity suggests consideration of HGF in the tumour microenvironment to select patients for clinical trials.
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| Overall design |
A549 and NCI-H596 cells linew were treated with HGF for 0, 3, 6 and 12 hours
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| Contributor(s) |
Cerqua M, Botti O, Arigoni M, Gioelli N, Serini G, Calogero R, Boccaccio C, Comoglio PM, Altintas DM |
| Citation(s) |
35636967 |
| Submission date |
Jan 25, 2022 |
| Last update date |
Aug 27, 2022 |
| Contact name |
Raffaele A Calogero |
| E-mail(s) |
raffaele.calogero@unito.it
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| Phone |
++39 0116706454
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| Organization name |
University of Torino
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| Department |
Molecular Biotechnology Center
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| Lab |
Bioinformatics and Genomics Unit
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| Street address |
Via Nizza 52
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| City |
Torino |
| State/province |
To |
| ZIP/Postal code |
10126 |
| Country |
Italy |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (16)
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| GSM5834865 |
MET wt 12h HGF A549S12wt12hHGF2 |
| GSM5834866 |
MET wt 3h HGF A549S3wt3hHGF1 |
| GSM5834867 |
MET wt 3h HGF A549S3wt3hHGF2 |
| GSM5834868 |
MET wt 6h HGF A549S6wt6hHGF1 |
| GSM5834869 |
MET wt 6h HGF A549S6wt6hHGF2 |
| GSM5834870 |
MET delta 14 exon no HGF NCIH596Sskp140h1 |
| GSM5834871 |
MET delta 14 exon no HGF NCIH596Sskp140h2 |
| GSM5834872 |
MET delta 14 exon 12 h HGF NCIH596S12skp1412hHGF1 |
| GSM5834873 |
MET delta 14 exon 12 h HGF NCIH596S12skp1412hHGF2 |
| GSM5834874 |
MET delta 14 exon 3h HGF NCIH596S3skp143hHGF1 |
| GSM5834875 |
MET delta 14 exon 3h HGF NCIH596S3skp143hHGF2 |
| GSM5834876 |
MET delta 14 exon 6h HGF NCIH596S6skp146hHGF1 |
| GSM5834877 |
MET delta 14 exon 6h HGF NCIH596S6skp146hHGF2 |
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| Relations |
| BioProject |
PRJNA800402 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE194382_counts.txt.gz |
798.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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