FIGURE 1.

LKB1 abrogates RTK activation in human cancer cell lines. LKB1-deficient lung cancer cell line (A549) was transfected with LacZ or LKB1 vectors, serum-starved, and stimulated with a mixture of growth factors prior to phospho-RTK screen. A, under basal, non-stimulatory conditions, RTK phosphorylation was undetected in both LacZ- and LKB1-expressing cells, as expected. B, however, upon growth factor stimulation, LKB1-expressing cells showed decreased phosphorylation of multiple RTKs compared with LacZ cells. C, LKB1-mediated phospho-RTK attenuation was observed in HeLaS3, another LKB1-deficient cancer cell line. D, in H1975 lung cancer cells that possess activating EGFR mutations, LKB1 overexpression blocked RTK activation compared with LacZ cells. E and F, confirmation of pY1234-HGFR and pY594-EphA2 dephosphorylation by LKB1 following stimulation with specific growth factor for the receptors. Cells were stimulated with 50 ng/ml of HGF or ephrin A1, respectively for 5 min.