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

被引：205

作者：

Carretero, Julian ^{[1
,2
]}

Shimamura, Takeshi ^{[1
,3
]}

Rikova, Klarisa ^{[4
]}

Jackson, Autumn L. ^{[5
]}

Wilkerson, Matthew D. ^{[5
]}

Borgman, Christa L. ^{[1
]}

Buttarazzi, Matthew S. ^{[1
,7
]}

Sanofsky, Benjamin A. ^{[1
,7
]}

McNamara, Kate L. ^{[1
,7
]}

Brandstetter, Kathleyn A. ^{[1
,7
]}

Walton, Zandra E. ^{[1
,7
]}

Gu, Ting-Lei ^{[4
]}

Silva, Jeffrey C. ^{[4
]}

Crosby, Katherine ^{[4
]}

Shapiro, Geoffrey I. ^{[1
,3
]}

Maira, Sauveur-Michel ^{[8
]}

Ji, Hongbin ^{[9
]}

Castrillon, Diego H. ^{[10
]}

Kim, Carla F. ^{[11
]}

Garcia-Echeverria, Carlos ^{[8
]}

Bardeesy, Nabeel ^{[12
]}

Sharpless, Norman E. ^{[5
,6
]}

Hayes, Neil D. ^{[5
]}

Kim, William Y. ^{[5
,6
]}

Engelman, Jeffrey A. ^{[12
]}

Wong, Kwok-Kin ^{[1
,3
,7
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Univ Valencia, Fac Med & Odontol, Dept Physiol, Valencia 46010, Spain

[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA

[4] Cell Signaling Technol Inc, Danvers, MA 01923 USA

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Dept Med & Genet, Chapel Hill, NC 27599 USA

[7] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA

[8] Novartis Inst Biomed Res, Oncol Dis Area, CH-4002 Basel, Switzerland

[9] Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[10] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[11] Childrens Hosp, Boston, MA 02115 USA

[12] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

来源：

CANCER CELL | 2010年 / 17卷 / 06期

关键词：

EXPRESSION; TUMORIGENESIS; SRC; SUPPRESSOR; MUTATIONS; ADENOCARCINOMA; INACTIVATION; SENSITIVITY; LKB1/STK11; SIGNATURES;

D O I：

10.1016/j.ccr.2010.04.026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：547 / 559

页数：13

共 45 条

[1] FatiGO:: a web tool for finding significant associations of Gene Ontology terms with groups of genes [J].