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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Metz, HE; Kargl, J; Busch, SE; Kim, KH; Kurland, BF; Abberbock, SR; Randolph-Habecker, J; Knoblaugh, SE; Kolls, JK; White, MF; Houghton, AM.
Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma.
Proc Natl Acad Sci U S A. 2016; 113(31):8795-8800 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kargl Julia Katharina
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Number of Figures: 10
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Abstract:
Insulin receptor substrate-1 (IRS-1) is a signaling adaptor protein that interfaces with many pathways activated in lung cancer. It has been assumed that IRS-1 promotes tumor growth through its ability to activate PI3K signaling downstream of the insulin-like growth factor receptor. Surprisingly, tumors with reduced IRS-1 staining in a human lung adenocarcinoma tissue microarray displayed a significant survival disadvantage, especially within the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant subgroup. Accordingly, adenoviral Cre recombinase (AdCre)-treated LSL-Kras/Irs-1(fl/fl) (Kras/Irs-1(-/-)) mice displayed increased tumor burden and mortality compared with controls. Mechanistically, IRS-1 deficiency promotes Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling via the IL-22 receptor, resulting in enhanced tumor-promoting inflammation. Treatment of Kras/Irs-1(+/+) and Kras/Irs-1(-/-) mice with JAK inhibitors significantly reduced tumor burden, most notably in the IRS-1-deficient group.
Find related publications in this database (using NLM MeSH Indexing)
A549 Cells -
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adult -
Aged -
Aged, 80 and over -
Animals -
Cell Line, Tumor -
Female -
Humans -
Insulin Receptor Substrate Proteins - deficiency
Insulin Receptor Substrate Proteins - genetics
Insulin Receptor Substrate Proteins - metabolism
Kaplan-Meier Estimate -
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male -
Mice, Knockout -
Middle Aged -
Mutation -
Phenotype -
Proto-Oncogene Proteins p21(ras) - genetics
Proto-Oncogene Proteins p21(ras) - metabolism
Receptors, Interleukin - genetics
Receptors, Interleukin - metabolism
Signal Transduction - genetics

Find related publications in this database (Keywords)
insulin receptor substrate-1
lung
adenocarcinoma
Kras
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