Language:

Integrative Genomic and Proteomic Analyses Identify Targets for Lkb1-Deficient Metastatic Lung Tumors

Cancer cell, 2010-06, Vol.17 (6), p.547-559 [Peer Reviewed Journal]

2010 Elsevier Inc. ;Copyright 2010 Elsevier Inc. All rights reserved. ;2010 Elsevier Inc. All rights reserved. 2010 ;ISSN: 1535-6108 ;EISSN: 1878-3686 ;DOI: 10.1016/j.ccr.2010.04.026 ;PMID: 20541700

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Integrative Genomic and Proteomic Analyses Identify Targets for Lkb1-Deficient Metastatic Lung Tumors
Author: Carretero, Julian ; Shimamura, Takeshi ; Rikova, Klarisa ; Jackson, Autumn L. ; Wilkerson, Matthew D. ; Borgman, Christa L. ; Buttarazzi, Matthew S. ; Sanofsky, Benjamin A. ; McNamara, Kate L. ; Brandstetter, Kathleyn A. ; Walton, Zandra E. ; Gu, Ting-Lei ; Silva, Jeffrey C. ; Crosby, Katherine ; Shapiro, Geoffrey I. ; Maira, Sauveur-Michel ; Ji, Hongbin ; Castrillon, Diego H. ; Kim, Carla F. ; García-Echeverría, Carlos ; Bardeesy, Nabeel ; Sharpless, Norman E. ; Hayes, Neil D. ; Kim, William Y. ; Engelman, Jeffrey A. ; Wong, Kwok-Kin
Subjects: Animals ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cell Adhesion - genetics ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Transdifferentiation - genetics ; CELLCYCLE ; Drug Therapy, Combination ; Enzyme Inhibitors - therapeutic use ; Female ; Focal Adhesion Protein-Tyrosine Kinases - antagonists & inhibitors ; Focal Adhesion Protein-Tyrosine Kinases - genetics ; Focal Adhesion Protein-Tyrosine Kinases - metabolism ; Focal Adhesions - genetics ; Focal Adhesions - metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic - genetics ; Genomics ; Humans ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; MAP Kinase Kinase 1 - antagonists & inhibitors ; MAP Kinase Kinase 2 - antagonists & inhibitors ; Mice ; Mice, Mutant Strains ; Mice, Nude ; Neoplasm Metastasis - drug therapy ; Neoplasm Metastasis - genetics ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphorylation - genetics ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - deficiency ; Protein-Serine-Threonine Kinases - genetics ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Proteomics ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins p21(ras) - genetics ; ras Proteins - genetics ; RNA Interference ; Signal Transduction - drug effects ; Signal Transduction - genetics ; SIGNALING ; src-Family Kinases - antagonists & inhibitors ; src-Family Kinases - genetics ; src-Family Kinases - metabolism ; TOR Serine-Threonine Kinases ; Up-Regulation - genetics ; Xenograft Model Antitumor Assays
Is Part Of: Cancer cell, 2010-06, Vol.17 (6), p.547-559
Description: In mice, Lkb1 deletion and activation of Kras G12D results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment. ► Lkb1 − / − metastatic lung tumors present unique gene signature with prognostic value in human NSCLC ► Lkb1-deficient metastases have upregulation of EMT-, SRC-, and FAK-associated gene signatures. ► Phospho-proteomics analyses of LKB1-deficient cells identify activation of SFKs and FAK. ► PI3K-mTOR, MEK, and SFKs combined inhibition is effective against Lkb1/kras mutant lung tumors.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1535-6108
EISSN: 1878-3686
DOI: 10.1016/j.ccr.2010.04.026
PMID: 20541700
Source: Cell Press Free Archives
MEDLINE

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Integrative Genomic and Proteomic Analyses Identify Targets for Lkb1-Deficient Metastatic Lung Tumors

2010 Elsevier Inc. ;Copyright 2010 Elsevier Inc. All rights reserved. ;2010 Elsevier Inc. All rights reserved. 2010 ;ISSN: 1535-6108 ;EISSN: 1878-3686 ;DOI: 10.1016/j.ccr.2010.04.026 ;PMID: 20541700

Searching Remote Databases, Please Wait