Author/Authors :
Carretero، نويسنده , , Julian and Shimamura، نويسنده , , Takeshi and Rikova، نويسنده , , Klarisa and Jackson، نويسنده , , Autumn L. and Wilkerson، نويسنده , , Matthew D. and Borgman، نويسنده , , Christa L. and Buttarazzi، نويسنده , , Matthew S. and Sanofsky، نويسنده , , Benjamin A. and McNamara، نويسنده , , Kate L. and Brandstetter، نويسنده , , Kathleyn A. and Walton، نويسنده , , Zandra E. and Gu، نويسنده , , Ting-Lei and Silva، نويسنده , , Jeffrey C. and Crosby، نويسنده , , Katherine and Shapiro، نويسنده , , Geoffrey I. and Maira، نويسنده , , Sauveur-Michel and Ji، نويسنده , , Hongbin and Castrillon، نويسنده , , Diego H. and Kim، نويسنده , , Carla F. and Garcيa-Echeverrيa، نويسنده , , Carlos and Bardeesy، نويسنده , , Nabeel and Sharpless، نويسنده , , Norman E. and Hayes، نويسنده , , Neil D. and Kim، نويسنده , , William Y. and Engelman، نويسنده , , Jeffrey A. and Wong، نويسنده , , Kwok-Kin، نويسنده ,
Abstract :
Summary
e, Lkb1 deletion and activation of KrasG12D 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.
