Diacylglycerol kinase n modualtes oncogenic properties of lung cancer cells
Clin. transl. oncol. (Print)
; 16(1): 29-35, ene. 2014. ilus
Article
in English
| IBECS
| ID: ibc-127516
Responsible library:
ES1.1
Localization: BNCS
ABSTRACT
PURPOSE:
Lung cancer is a leading cause of cancer deaths and efforts are underway to identify novel therapies to treat these tumors. Diacylglycerol kinase η (DGKη), an enzyme that phosphorylates diacylglycerol to form phosphatidic acid, has been shown to modulate MAPK signaling downstream of EGFR, which is an oncogenic driver in some lung cancers. Since mutations in EGFR and K-Ras are common in lung cancer, we hypothesized that limiting the function of DGKη would attenuate oncogenic properties of lung cancer cells.METHODS:
We determined the expression levels of DGKη in a mouse models of mutant EGFR and K-Ras lung cancer and in human lung cancer cell lines with activating mutations in either EGFR or K-Ras. We also tested the effects of shRNA-mediated depletion of DGKη in lung cancer cells and tested if DGKη depletion augmented the effects of afatinib, a new generation EGFR inhibitor.RESULTS:
DGKη was expressed in malignant epithelium from mice with mutant EGFR or K-Ras lung cancer. It was also expressed in human lung cancer cell lines with EGFR or K-Ras mutations. Depleting DGKη in lung cancer cell lines, harboring mutant EGFR, reduced their growth on plastic and in soft agar and also augmented the effects of afatinib, an EGFR inhibitor. DGKη depletion also reduced growth of one of two lung cancer cell lines that harbored mutant K-Ras.CONCLUSIONS:
Our data indicate that DGKη is a potential therapeutic target in lung cancers, especially those harboring EGFR mutations. Our findings warrant further studies to examine the effects of limiting its function in vivo (AU)RESUMEN
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Collection:
National databases
/
Spain
Health context:
SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases
Health problem:
Other Respiratory Diseases
/
Trachea, Bronchus, Lung Cancers
Database:
IBECS
Main subject:
Genes, ras
/
Genes, erbB-1
/
Reverse Transcriptase Polymerase Chain Reaction
/
Cell Line, Tumor
/
Lung Neoplasms
/
Mutation
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Clin. transl. oncol. (Print)
Year:
2014
Document type:
Article
Institution/Affiliation country:
University od Utah/USA
/
University of Utah/USA