RGD Reference Report - IER2-induced senescence drives melanoma invasion through osteopontin. - Rat Genome Database

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IER2-induced senescence drives melanoma invasion through osteopontin.

Authors: Kyjacova, Lenka  Saup, Rafael  Rönsch, Kerstin  Wallbaum, Sabine  Dukowic-Schulze, Stefanie  Foss, Amelia  Scherer, Sandra D  Rothley, Melanie  Neeb, Antje  Grau, Nicole  Thiele, Wilko  Thaler, Sonja  Cremers, Natascha  Sticht, Carsten  Gretz, Norbert  Garvalov, Boyan K  Utikal, Jochen  Sleeman, Jonathan P 
Citation: Kyjacova L, etal., Oncogene. 2021 Nov;40(47):6494-6512. doi: 10.1038/s41388-021-02027-6. Epub 2021 Oct 5.
RGD ID: 153323325
Pubmed: PMID:34611309   (View Abstract at PubMed)
PMCID: PMC8616759   (View Article at PubMed Central)
DOI: DOI:10.1038/s41388-021-02027-6   (Journal Full-text)

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IER2Humanmelanoma disease_progressionIEP mRNA:increased expression:skin (human)RGD 
Ier2Ratmelanoma disease_progressionISOIER2 (Homo sapiens)mRNA:increased expression:skin (human)RGD 
Ier2Mousemelanoma disease_progressionISOIER2 (Homo sapiens)mRNA:increased expression:skin (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ier2  (immediate early response 2)

Genes (Mus musculus)
Ier2  (immediate early response 2)

Genes (Homo sapiens)
IER2  (immediate early response 2)


Additional Information