Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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
Doi: 10.1073/pnas.1601989113
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- Co-authors Med Uni Graz
- Kargl Julia
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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 -
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- 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
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- Phenotype -
- Proto-Oncogene Proteins p21(ras) - genetics
- Proto-Oncogene Proteins p21(ras) - metabolism
- Receptors, Interleukin - genetics
- Receptors, Interleukin - metabolism
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- Find related publications in this database (Keywords)
- insulin receptor substrate-1
- lung
- adenocarcinoma
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