RGD Reference Report - A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation.

Authors: Ray, Debleena  Yun, Yu Chye  Idris, Muhammad  Cheng, Shanshan  Boot, Arnoud  Iain, Tan Bee Huat  Rozen, Steven G  Tan, Patrick  Epstein, David M 
Citation: Ray D, etal., Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16391-16400. doi: 10.1073/pnas.2002499117. Epub 2020 Jun 29.
RGD ID: 155230826
Pubmed: PMID:32601196   (View Abstract at PubMed)
PMCID: PMC7368273   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.2002499117   (Journal Full-text)

Master splicing regulator MBNL1 shapes large transcriptomic changes that drive cellular differentiation during development. Here we demonstrate that MBNL1 is a suppressor of tumor dedifferentiation. We surveyed MBNL1 expression in matched tumor/normal pairs across The Cancer Genome Atlas and found that MBNL1 was down-regulated in several common cancers. Down-regulation of MBNL1 predicted poor overall survival in breast, lung, and stomach adenocarcinomas and increased relapse and distant metastasis in triple-negative breast cancer. Down-regulation of MBNL1 led to increased tumorigenic and stem/progenitor-like properties in vitro and in vivo. A discrete set of alternative splicing events (ASEs) are shared between MBNL1-low cancers and embryonic stem cells including a MAP2K7∆exon2 splice variant that leads to increased stem/progenitor-like properties via JNK activation. Accordingly, JNK inhibition is capable of reversing MAP2K7∆exon2-driven tumor dedifferentiation in MBNL1-low cancer cells. Our work elucidates an alternative-splicing mechanism that drives tumor dedifferentiation and identifies biomarkers that predict enhanced susceptibility to JNK inhibition.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer  HEP 155230826mRNA:splice variant:exon 2: (human)RGD 
breast cancer  ISOMAP2K7 (Homo sapiens)155230826; 155230826mRNA:splice variant:exon 2: (human)RGD 
colon cancer  HEP 155230826mRNA:splice variant:exon 2: (human)RGD 
colon cancer  ISOMAP2K7 (Homo sapiens)155230826; 155230826mRNA:splice variant:exon 2: (human)RGD 
prostate cancer  HEP 155230826mRNA:splice variant:exon 2: (human)RGD 
prostate cancer  ISOMAP2K7 (Homo sapiens)155230826; 155230826mRNA:splice variant:exon 2: (human)RGD 
stomach cancer  HEP 155230826mRNA:splice variant:exon 2: (human)RGD 
stomach cancer  ISOMAP2K7 (Homo sapiens)155230826; 155230826mRNA:splice variant:exon 2: (human)RGD 
urinary bladder cancer  HEP 155230826mRNA:splice variant:exon 2: (human)RGD 
urinary bladder cancer  ISOMAP2K7 (Homo sapiens)155230826; 155230826mRNA:splice variant:exon 2: (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k7  (mitogen activated protein kinase kinase 7)

Genes (Mus musculus)
Map2k7  (mitogen-activated protein kinase kinase 7)

Genes (Homo sapiens)
MAP2K7  (mitogen-activated protein kinase kinase 7)


Additional Information